|
Inhibition of mTOR
|
None
|
0.8
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Allosteric and ATP-competitive kinase inhibitors of mTOR for cancer treatment.
Year : 2010
Volume : 20
Issue : 15
First Page : 4308
Last Page : 4312
Authors : García-Echeverría C.
Abstract : Over the past few years a number of components of the PI3K/mTOR pathway have been the subject of intense drug discovery activities both in pharmaceutical companies and in academia. This review article summarizes progress made in the identification and development of allosteric and ATP-competitive kinase inhibitors of mTOR and their potential therapeutic use in oncology.
|
Inhibition of mTORC2 in human MDA-MB-468 cells assessed as reduction of AKT phosphorylation at Ser473 after 2 hrs
|
Homo sapiens
|
24.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.
Year : 2013
Volume : 23
Issue : 5
First Page : 1212
Last Page : 1216
Authors : Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M.
Abstract : The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC(50), led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
|
Inhibition of mTORC1 in human MDA-MB-468 cells assessed as reduction of pS6 phosphorylation at Ser235/236 after 2 hrs
|
Homo sapiens
|
27.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.
Year : 2013
Volume : 23
Issue : 5
First Page : 1212
Last Page : 1216
Authors : Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M.
Abstract : The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC(50), led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
|
Inhibition of recombinant FLAG-tagged mTOR (1362 to 2549) (unknown origin) expressed in HEK293 cells
|
Homo sapiens
|
0.13
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014.
Year : 2013
Volume : 23
Issue : 5
First Page : 1212
Last Page : 1216
Authors : Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M.
Abstract : The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC(50), led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
|
SANGER: Inhibition of human NCI-H1563 cell growth in a cell viability assay.
|
Homo sapiens
|
789.26
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1573 cell growth in a cell viability assay.
|
Homo sapiens
|
902.29
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1581 cell growth in a cell viability assay.
|
Homo sapiens
|
189.66
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1623 cell growth in a cell viability assay.
|
Homo sapiens
|
762.61
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1648 cell growth in a cell viability assay.
|
Homo sapiens
|
701.73
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1770 cell growth in a cell viability assay.
|
Homo sapiens
|
802.1
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1792 cell growth in a cell viability assay.
|
Homo sapiens
|
971.01
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1793 cell growth in a cell viability assay.
|
Homo sapiens
|
534.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H209 cell growth in a cell viability assay.
|
Homo sapiens
|
54.53
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H2347 cell growth in a cell viability assay.
|
Homo sapiens
|
824.01
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H2452 cell growth in a cell viability assay.
|
Homo sapiens
|
619.17
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H28 cell growth in a cell viability assay.
|
Homo sapiens
|
586.75
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H292 cell growth in a cell viability assay.
|
Homo sapiens
|
291.64
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H460 cell growth in a cell viability assay.
|
Homo sapiens
|
505.97
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H520 cell growth in a cell viability assay.
|
Homo sapiens
|
348.34
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H522 cell growth in a cell viability assay.
|
Homo sapiens
|
629.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H650 cell growth in a cell viability assay.
|
Homo sapiens
|
791.44
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H720 cell growth in a cell viability assay.
|
Homo sapiens
|
29.38
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H747 cell growth in a cell viability assay.
|
Homo sapiens
|
759.91
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-SNU-1 cell growth in a cell viability assay.
|
Homo sapiens
|
323.31
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NEC8 cell growth in a cell viability assay.
|
Homo sapiens
|
416.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NKM-1 cell growth in a cell viability assay.
|
Homo sapiens
|
200.29
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NOS-1 cell growth in a cell viability assay.
|
Homo sapiens
|
410.74
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NTERA-S-cl-D1 cell growth in a cell viability assay.
|
Homo sapiens
|
700.63
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NUGC-3 cell growth in a cell viability assay.
|
Homo sapiens
|
706.91
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OAW-42 cell growth in a cell viability assay.
|
Homo sapiens
|
591.62
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OCUB-M cell growth in a cell viability assay.
|
Homo sapiens
|
826.75
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OE33 cell growth in a cell viability assay.
|
Homo sapiens
|
799.14
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OMC-1 cell growth in a cell viability assay.
|
Homo sapiens
|
727.38
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OVCAR-4 cell growth in a cell viability assay.
|
Homo sapiens
|
819.11
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OVCAR-5 cell growth in a cell viability assay.
|
Homo sapiens
|
429.33
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human P30-OHK cell growth in a cell viability assay.
|
Homo sapiens
|
327.05
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PA-1 cell growth in a cell viability assay.
|
Homo sapiens
|
336.19
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PANC-08-13 cell growth in a cell viability assay.
|
Homo sapiens
|
573.89
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PC-14 cell growth in a cell viability assay.
|
Homo sapiens
|
589.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PC-3 cell growth in a cell viability assay.
|
Homo sapiens
|
722.3
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PFSK-1 cell growth in a cell viability assay.
|
Homo sapiens
|
830.39
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human PSN1 cell growth in a cell viability assay.
|
Homo sapiens
|
770.57
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human QIMR-WIL cell growth in a cell viability assay.
|
Homo sapiens
|
451.5
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RKO cell growth in a cell viability assay.
|
Homo sapiens
|
868.17
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RPMI-7951 cell growth in a cell viability assay.
|
Homo sapiens
|
735.33
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RPMI-8226 cell growth in a cell viability assay.
|
Homo sapiens
|
285.89
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RPMI-8866 cell growth in a cell viability assay.
|
Homo sapiens
|
858.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RS4-11 cell growth in a cell viability assay.
|
Homo sapiens
|
759.43
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RT-112 cell growth in a cell viability assay.
|
Homo sapiens
|
849.37
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RVH-421 cell growth in a cell viability assay.
|
Homo sapiens
|
636.39
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RXF393 cell growth in a cell viability assay.
|
Homo sapiens
|
928.97
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human Ramos-2G6-4C10 cell growth in a cell viability assay.
|
Homo sapiens
|
169.83
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SBC-1 cell growth in a cell viability assay.
|
Homo sapiens
|
45.81
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SCC-4 cell growth in a cell viability assay.
|
Homo sapiens
|
585.41
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SF126 cell growth in a cell viability assay.
|
Homo sapiens
|
887.14
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SF295 cell growth in a cell viability assay.
|
Homo sapiens
|
685.07
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SJSA-1 cell growth in a cell viability assay.
|
Homo sapiens
|
445.54
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-LU-1 cell growth in a cell viability assay.
|
Homo sapiens
|
392.08
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-MEL-2 cell growth in a cell viability assay.
|
Homo sapiens
|
641.53
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-MEL-28 cell growth in a cell viability assay.
|
Homo sapiens
|
559.1
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-MES-1 cell growth in a cell viability assay.
|
Homo sapiens
|
438.48
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-NEP-1 cell growth in a cell viability assay.
|
Homo sapiens
|
625.02
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SK-OV-3 cell growth in a cell viability assay.
|
Homo sapiens
|
671.87
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SN12C cell growth in a cell viability assay.
|
Homo sapiens
|
806.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SNU-423 cell growth in a cell viability assay.
|
Homo sapiens
|
814.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SNU-449 cell growth in a cell viability assay.
|
Homo sapiens
|
959.24
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW13 cell growth in a cell viability assay.
|
Homo sapiens
|
983.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW1710 cell growth in a cell viability assay.
|
Homo sapiens
|
631.67
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW780 cell growth in a cell viability assay.
|
Homo sapiens
|
575.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW962 cell growth in a cell viability assay.
|
Homo sapiens
|
471.9
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW982 cell growth in a cell viability assay.
|
Homo sapiens
|
685.01
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human T47D cell growth in a cell viability assay.
|
Homo sapiens
|
274.75
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human 22RV1 cell growth in a cell viability assay.
|
Homo sapiens
|
707.17
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human 697 cell growth in a cell viability assay.
|
Homo sapiens
|
273.67
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human 8305C cell growth in a cell viability assay.
|
Homo sapiens
|
707.55
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A101D cell growth in a cell viability assay.
|
Homo sapiens
|
489.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A204 cell growth in a cell viability assay.
|
Homo sapiens
|
189.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A2058 cell growth in a cell viability assay.
|
Homo sapiens
|
973.6
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A3-KAW cell growth in a cell viability assay.
|
Homo sapiens
|
297.4
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A375 cell growth in a cell viability assay.
|
Homo sapiens
|
751.93
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A427 cell growth in a cell viability assay.
|
Homo sapiens
|
961.98
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A431 cell growth in a cell viability assay.
|
Homo sapiens
|
831.16
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A549 cell growth in a cell viability assay.
|
Homo sapiens
|
195.5
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A704 cell growth in a cell viability assay.
|
Homo sapiens
|
817.98
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ACN cell growth in a cell viability assay.
|
Homo sapiens
|
942.77
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human AN3-CA cell growth in a cell viability assay.
|
Homo sapiens
|
79.51
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ATN-1 cell growth in a cell viability assay.
|
Homo sapiens
|
705.9
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human AsPC-1 cell growth in a cell viability assay.
|
Homo sapiens
|
737.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BB65-RCC cell growth in a cell viability assay.
|
Homo sapiens
|
308.05
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BCPAP cell growth in a cell viability assay.
|
Homo sapiens
|
587.91
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BEN cell growth in a cell viability assay.
|
Homo sapiens
|
212.93
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BFTC-905 cell growth in a cell viability assay.
|
Homo sapiens
|
621.26
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BHT-101 cell growth in a cell viability assay.
|
Homo sapiens
|
407.87
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BHY cell growth in a cell viability assay.
|
Homo sapiens
|
887.34
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BPH-1 cell growth in a cell viability assay.
|
Homo sapiens
|
883.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BV-173 cell growth in a cell viability assay.
|
Homo sapiens
|
90.61
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BxPC-3 cell growth in a cell viability assay.
|
Homo sapiens
|
888.33
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human C-33-A cell growth in a cell viability assay.
|
Homo sapiens
|
904.42
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human C32 cell growth in a cell viability assay.
|
Homo sapiens
|
724.84
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAKI-1 cell growth in a cell viability assay.
|
Homo sapiens
|
746.29
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-120 cell growth in a cell viability assay.
|
Homo sapiens
|
860.41
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-12T cell growth in a cell viability assay.
|
Homo sapiens
|
780.29
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-33 cell growth in a cell viability assay.
|
Homo sapiens
|
864.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-39 cell growth in a cell viability assay.
|
Homo sapiens
|
522.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-51 cell growth in a cell viability assay.
|
Homo sapiens
|
196.51
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAL-62 cell growth in a cell viability assay.
|
Homo sapiens
|
799.24
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human TE-5 cell growth in a cell viability assay.
|
Homo sapiens
|
684.05
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human TI-73 cell growth in a cell viability assay.
|
Homo sapiens
|
456.86
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human TYK-nu cell growth in a cell viability assay.
|
Homo sapiens
|
318.64
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human U-2-OS cell growth in a cell viability assay.
|
Homo sapiens
|
759.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human UACC-893 cell growth in a cell viability assay.
|
Homo sapiens
|
928.55
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human VA-ES-BJ cell growth in a cell viability assay.
|
Homo sapiens
|
342.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human VM-CUB-1 cell growth in a cell viability assay.
|
Homo sapiens
|
472.86
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human VMRC-RCZ cell growth in a cell viability assay.
|
Homo sapiens
|
784.82
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human WM-115 cell growth in a cell viability assay.
|
Homo sapiens
|
689.24
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human YH-13 cell growth in a cell viability assay.
|
Homo sapiens
|
549.38
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CAMA-1 cell growth in a cell viability assay.
|
Homo sapiens
|
621.52
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CHL-1 cell growth in a cell viability assay.
|
Homo sapiens
|
327.03
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CHP-212 cell growth in a cell viability assay.
|
Homo sapiens
|
436.97
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human COLO-684 cell growth in a cell viability assay.
|
Homo sapiens
|
457.26
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human COLO-800 cell growth in a cell viability assay.
|
Homo sapiens
|
698.13
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human COR-L88 cell growth in a cell viability assay.
|
Homo sapiens
|
422.67
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CP50-MEL-B cell growth in a cell viability assay.
|
Homo sapiens
|
883.84
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CTB-1 cell growth in a cell viability assay.
|
Homo sapiens
|
272.15
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human CTV-1 cell growth in a cell viability assay.
|
Homo sapiens
|
86.41
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human Ca9-22 cell growth in a cell viability assay.
|
Homo sapiens
|
787.36
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human D-283MED cell growth in a cell viability assay.
|
Homo sapiens
|
147.23
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DB cell growth in a cell viability assay.
|
Homo sapiens
|
500.21
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DEL cell growth in a cell viability assay.
|
Homo sapiens
|
967.73
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DMS-114 cell growth in a cell viability assay.
|
Homo sapiens
|
936.77
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DMS-273 cell growth in a cell viability assay.
|
Homo sapiens
|
769.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DOHH-2 cell growth in a cell viability assay.
|
Homo sapiens
|
793.3
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DOK cell growth in a cell viability assay.
|
Homo sapiens
|
513.33
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human DU-4475 cell growth in a cell viability assay.
|
Homo sapiens
|
80.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ECC10 cell growth in a cell viability assay.
|
Homo sapiens
|
350.35
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EFM-19 cell growth in a cell viability assay.
|
Homo sapiens
|
708.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EFO-27 cell growth in a cell viability assay.
|
Homo sapiens
|
679.79
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EGI-1 cell growth in a cell viability assay.
|
Homo sapiens
|
135.31
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EM-2 cell growth in a cell viability assay.
|
Homo sapiens
|
341.88
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EPLC-272H cell growth in a cell viability assay.
|
Homo sapiens
|
430.77
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ES1 cell growth in a cell viability assay.
|
Homo sapiens
|
555.18
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ES4 cell growth in a cell viability assay.
|
Homo sapiens
|
453.36
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ES5 cell growth in a cell viability assay.
|
Homo sapiens
|
93.5
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ES7 cell growth in a cell viability assay.
|
Homo sapiens
|
273.83
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ES8 cell growth in a cell viability assay.
|
Homo sapiens
|
365.53
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ETK-1 cell growth in a cell viability assay.
|
Homo sapiens
|
893.72
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EW-18 cell growth in a cell viability assay.
|
Homo sapiens
|
140.73
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EW-22 cell growth in a cell viability assay.
|
Homo sapiens
|
684.44
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EW-3 cell growth in a cell viability assay.
|
Homo sapiens
|
40.56
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EoL-1-cell cell growth in a cell viability assay.
|
Homo sapiens
|
65.69
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human G-401 cell growth in a cell viability assay.
|
Homo sapiens
|
309.86
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human G-402 cell growth in a cell viability assay.
|
Homo sapiens
|
99.8
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human GAMG cell growth in a cell viability assay.
|
Homo sapiens
|
556.58
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human GCIY cell growth in a cell viability assay.
|
Homo sapiens
|
457.54
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human GR-ST cell growth in a cell viability assay.
|
Homo sapiens
|
530.15
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human H4 cell growth in a cell viability assay.
|
Homo sapiens
|
600.94
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human H9 cell growth in a cell viability assay.
|
Homo sapiens
|
66.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HAL-01 cell growth in a cell viability assay.
|
Homo sapiens
|
202.97
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HCC1419 cell growth in a cell viability assay.
|
Homo sapiens
|
869.28
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HCC1569 cell growth in a cell viability assay.
|
Homo sapiens
|
852.07
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HCC1806 cell growth in a cell viability assay.
|
Homo sapiens
|
932.56
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HCC2218 cell growth in a cell viability assay.
|
Homo sapiens
|
206.88
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HD-MY-Z cell growth in a cell viability assay.
|
Homo sapiens
|
840.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HGC-27 cell growth in a cell viability assay.
|
Homo sapiens
|
264.14
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HH cell growth in a cell viability assay.
|
Homo sapiens
|
80.09
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HL-60 cell growth in a cell viability assay.
|
Homo sapiens
|
603.51
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HLE cell growth in a cell viability assay.
|
Homo sapiens
|
748.44
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HO-1-N-1 cell growth in a cell viability assay.
|
Homo sapiens
|
680.64
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HOS cell growth in a cell viability assay.
|
Homo sapiens
|
571.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HPAF-II cell growth in a cell viability assay.
|
Homo sapiens
|
807.94
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HSC-3 cell growth in a cell viability assay.
|
Homo sapiens
|
429.08
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HT cell growth in a cell viability assay.
|
Homo sapiens
|
293.8
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HT-1080 cell growth in a cell viability assay.
|
Homo sapiens
|
525.43
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HTC-C3 cell growth in a cell viability assay.
|
Homo sapiens
|
731.72
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human Hs-578-T cell growth in a cell viability assay.
|
Homo sapiens
|
598.51
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HuH-7 cell growth in a cell viability assay.
|
Homo sapiens
|
433.72
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HuO-3N1 cell growth in a cell viability assay.
|
Homo sapiens
|
383.79
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human HuO9 cell growth in a cell viability assay.
|
Homo sapiens
|
406.67
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human IA-LM cell growth in a cell viability assay.
|
Homo sapiens
|
596.09
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human IGROV-1 cell growth in a cell viability assay.
|
Homo sapiens
|
674.5
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human J-RT3-T3-5 cell growth in a cell viability assay.
|
Homo sapiens
|
531.95
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human JVM-3 cell growth in a cell viability assay.
|
Homo sapiens
|
462.92
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KARPAS-45 cell growth in a cell viability assay.
|
Homo sapiens
|
33.71
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KE-37 cell growth in a cell viability assay.
|
Homo sapiens
|
432.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KG-1 cell growth in a cell viability assay.
|
Homo sapiens
|
568.84
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KGN cell growth in a cell viability assay.
|
Homo sapiens
|
610.49
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KNS-62 cell growth in a cell viability assay.
|
Homo sapiens
|
505.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KP-N-YS cell growth in a cell viability assay.
|
Homo sapiens
|
430.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KU-19-19 cell growth in a cell viability assay.
|
Homo sapiens
|
851.21
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KU812 cell growth in a cell viability assay.
|
Homo sapiens
|
80.43
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KYSE-140 cell growth in a cell viability assay.
|
Homo sapiens
|
781.68
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KYSE-150 cell growth in a cell viability assay.
|
Homo sapiens
|
661.86
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KYSE-450 cell growth in a cell viability assay.
|
Homo sapiens
|
827.25
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human L-363 cell growth in a cell viability assay.
|
Homo sapiens
|
390.26
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LAMA-84 cell growth in a cell viability assay.
|
Homo sapiens
|
180.32
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LB1047-RCC cell growth in a cell viability assay.
|
Homo sapiens
|
340.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LB2241-RCC cell growth in a cell viability assay.
|
Homo sapiens
|
301.98
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LC-2-ad cell growth in a cell viability assay.
|
Homo sapiens
|
220.84
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LK-2 cell growth in a cell viability assay.
|
Homo sapiens
|
268.24
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LNCaP-Clone-FGC cell growth in a cell viability assay.
|
Homo sapiens
|
353.14
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LOXIMVI cell growth in a cell viability assay.
|
Homo sapiens
|
551.23
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LU-139 cell growth in a cell viability assay.
|
Homo sapiens
|
23.31
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LU-99A cell growth in a cell viability assay.
|
Homo sapiens
|
776.49
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LXF-289 cell growth in a cell viability assay.
|
Homo sapiens
|
250.41
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LoVo cell growth in a cell viability assay.
|
Homo sapiens
|
202.02
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human M14 cell growth in a cell viability assay.
|
Homo sapiens
|
471.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MC-IXC cell growth in a cell viability assay.
|
Homo sapiens
|
727.18
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MCF7 cell growth in a cell viability assay.
|
Homo sapiens
|
405.3
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MDA-MB-157 cell growth in a cell viability assay.
|
Homo sapiens
|
678.1
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MDA-MB-175-VII cell growth in a cell viability assay.
|
Homo sapiens
|
577.41
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MDA-MB-361 cell growth in a cell viability assay.
|
Homo sapiens
|
508.7
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ME-180 cell growth in a cell viability assay.
|
Homo sapiens
|
146.81
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MEL-HO cell growth in a cell viability assay.
|
Homo sapiens
|
677.52
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MFE-280 cell growth in a cell viability assay.
|
Homo sapiens
|
430.32
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MFM-223 cell growth in a cell viability assay.
|
Homo sapiens
|
426.17
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MG-63 cell growth in a cell viability assay.
|
Homo sapiens
|
274.07
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MHH-ES-1 cell growth in a cell viability assay.
|
Homo sapiens
|
834.57
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MHH-PREB-1 cell growth in a cell viability assay.
|
Homo sapiens
|
747.36
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MIA-PaCa-2 cell growth in a cell viability assay.
|
Homo sapiens
|
929.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human ML-2 cell growth in a cell viability assay.
|
Homo sapiens
|
584.78
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MN-60 cell growth in a cell viability assay.
|
Homo sapiens
|
678.46
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MOLT-13 cell growth in a cell viability assay.
|
Homo sapiens
|
665.37
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MOLT-16 cell growth in a cell viability assay.
|
Homo sapiens
|
938.45
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MOLT-4 cell growth in a cell viability assay.
|
Homo sapiens
|
676.89
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MPP-89 cell growth in a cell viability assay.
|
Homo sapiens
|
469.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MSTO-211H cell growth in a cell viability assay.
|
Homo sapiens
|
577.51
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MV-4-11 cell growth in a cell viability assay.
|
Homo sapiens
|
103.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MZ2-MEL cell growth in a cell viability assay.
|
Homo sapiens
|
408.82
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NB14 cell growth in a cell viability assay.
|
Homo sapiens
|
164.47
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NB5 cell growth in a cell viability assay.
|
Homo sapiens
|
703.19
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NB69 cell growth in a cell viability assay.
|
Homo sapiens
|
135.0
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NBsusSR cell growth in a cell viability assay.
|
Homo sapiens
|
170.19
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1048 cell growth in a cell viability assay.
|
Homo sapiens
|
586.45
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1355 cell growth in a cell viability assay.
|
Homo sapiens
|
538.78
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H1437 cell growth in a cell viability assay.
|
Homo sapiens
|
606.19
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
Inhibition of mTORC1-mediated S6 phosphorylation at Ser235/236 residue in human MDA-MB-468 cells after 2 hrs by Acumen laser scanning cytometry
|
Homo sapiens
|
26.92
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of AZD3147: a potent, selective dual inhibitor of mTORC1 and mTORC2.
Year : 2015
Volume : 58
Issue : 5
First Page : 2326
Last Page : 2349
Authors : Pike KG, Morris J, Ruston L, Pass SL, Greenwood R, Williams EJ, Demeritt J, Culshaw JD, Gill K, Pass M, Finlay MR, Good CJ, Roberts CA, Currie GS, Blades K, Eden JM, Pearson SE.
Abstract : High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC50-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.
|
Inhibition of mTORC2-mediated AKT phosphorylation at Ser473 residue in human MDA-MB-468 cells after 2 hrs by Acumen laser scanning cytometry
|
Homo sapiens
|
23.99
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of AZD3147: a potent, selective dual inhibitor of mTORC1 and mTORC2.
Year : 2015
Volume : 58
Issue : 5
First Page : 2326
Last Page : 2349
Authors : Pike KG, Morris J, Ruston L, Pass SL, Greenwood R, Williams EJ, Demeritt J, Culshaw JD, Gill K, Pass M, Finlay MR, Good CJ, Roberts CA, Currie GS, Blades K, Eden JM, Pearson SE.
Abstract : High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC50-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.
|
Cytotoxicity against human Glioma cells (HF2303) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF2381) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF2476) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF2790) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF2876) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF2885) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Cytotoxicity against human Glioma cells (HF3013) after 72 hrs by CelltiterGlo assay
|
Homo sapiens
|
0.7
nM
|
|
Journal : ACS Med. Chem. Lett.
Title : High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma.
Year : 2015
Volume : 6
Issue : 8
First Page : 948
Last Page : 952
Authors : Quartararo CE, Reznik E, deCarvalho AC, Mikkelsen T, Stockwell BR.
Abstract : Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose-response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples.
|
Alternative Enzyme Assay: The assay used AlphaScreen technology (Gray et al., Analytical Biochemistry, 2003, 313: 234-245) to determine the ability of test compounds to inhibit phosphorylation by recombinant mTOR.Test compounds were prepared as 10 mM stock solutions in DMSO and diluted into water as required to give a range of final assay concentrations. Aliquots (2 ul) of each compound dilution were placed into a well of a Greiner 384-well low volume (LV) white polystyrene plate (Greiner Bio-one). A 10 ul mixture of recombinant purified mTOR enzyme, 1 uM biotinylated peptide substrate (Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2; Bachem UK Ltd), ATP (20 uM) in a buffer solution [comprising Tris-HCl pH7.4 buffer (50 mM), EGTA (0.1 mM), bovine serum albumin (0.5 mg/ml), DTT (1.25 mM) and manganese chloride (10 mM)] were added to the assay plates and incubated with compound for 2 hours at room temperature.
|
Homo sapiens
|
8.9
nM
|
|
Title : Pyrido-, pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors
Year : 2015
|
Antiproliferative activity against human A549 cells after 72 hrs by SRB assay
|
Homo sapiens
|
50.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Antiproliferative activity against human A375 cells after 72 hrs by SRB assay
|
Homo sapiens
|
120.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Antiproliferative activity against human MCF7 cells after 72 hrs by SRB assay
|
Homo sapiens
|
140.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Antiproliferative activity against human U87 cells after 72 hrs by SRB assay
|
Homo sapiens
|
190.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Antiproliferative activity against human NCI-H460 cells after 72 hrs by SRB assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of human PI3K p110alpha/p85alpha at 10 uM using phosphatidylinositol 4,5-bisphosphate as substrate after 30 mins by HTRF assay relative to control
|
Homo sapiens
|
70.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of human PI3K p110beta/p85alpha at 10 uM using phosphatidylinositol 4,5-bisphosphate as substrate after 30 mins by HTRF assay relative to control
|
Homo sapiens
|
12.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of human PI3K p120gamma at 10 uM using phosphatidylinositol 4,5-bisphosphate as substrate after 30 mins by HTRF assay relative to control
|
Homo sapiens
|
29.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of human PI3K p110delta/p85alpha at 10 uM using phosphatidylinositol 4,5-bisphosphate as substrate after 30 mins by HTRF assay relative to control
|
Homo sapiens
|
59.0
%
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of human N-terminal FLAG-tagged mTOR (1362-end residues) in presence of [gamma33P]ATP after 40 mins
|
Homo sapiens
|
4.0
nM
|
|
Journal : Eur J Med Chem
Title : Design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine derivatives as mTOR inhibitors.
Year : 2017
Volume : 129
First Page : 135
Last Page : 150
Authors : Mao B, Gao S, Weng Y, Zhang L, Zhang L.
Abstract : ATP-competitive mTOR inhibitors have been studied as potential antitumor agents. Based on the structure-activity relationship of known mTOR inhibitors, a series of novel imidazo[1,2-b]pyridazine derivatives were synthesized and characterized. The anti-proliferative activities of these compounds were evaluated by SRB assay against six human cancer cell lines. Imidazo[1,2-b]pyridazine diaryl urea derivatives A15-A24 exhibited significant anti-proliferative activity especially against non-small cell lung cancer A549 and H460 with IC50 values ranging from 0.02 μM to 20.7 μM. Among them, compounds A17 and A18 showed mTOR inhibitory activity with IC50 of 0.067 μM and 0.062 μM, respectively. A more detailed analysis of compounds A17 and A18 showed that they induced G1-phase cell cycle arrest and suppressed the phosphorylation of AKT and S6 at cellular level. Moreover, obvious anticancer effect of A17 in vivo was observed in established nude mice A549 xenograft model.
|
Inhibition of mTOR (unknown origin) using ULight-4E-BP1 peptide substrate measured after 1 hr by Lance Ultra assay
|
Homo sapiens
|
8.0
nM
|
|
Journal : Bioorg Med Chem
Title : Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity.
Year : 2018
Volume : 26
Issue : 14
First Page : 3992
Last Page : 4000
Authors : Liu Y, Xia Q, Fang L.
Abstract : Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC50 values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially 3j whose potency against SKOV3 was 8-fold higher than the positive control AZD8055. In vitro metabolic stability study found that 3j had a comparable stability to that of AZD8055. More importantly, 3j showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.
|
Antiproliferative activity against human U87MG cells assessed as reduction in cell viability after 48 hrs by CCK8 assay
|
Homo sapiens
|
21.2
nM
|
|
Journal : Bioorg Med Chem
Title : Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity.
Year : 2018
Volume : 26
Issue : 14
First Page : 3992
Last Page : 4000
Authors : Liu Y, Xia Q, Fang L.
Abstract : Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC50 values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially 3j whose potency against SKOV3 was 8-fold higher than the positive control AZD8055. In vitro metabolic stability study found that 3j had a comparable stability to that of AZD8055. More importantly, 3j showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.
|
Antiproliferative activity against human MCF7 cells assessed as reduction in cell viability after 48 hrs by CCK8 assay
|
Homo sapiens
|
27.0
nM
|
|
Journal : Bioorg Med Chem
Title : Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity.
Year : 2018
Volume : 26
Issue : 14
First Page : 3992
Last Page : 4000
Authors : Liu Y, Xia Q, Fang L.
Abstract : Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC50 values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially 3j whose potency against SKOV3 was 8-fold higher than the positive control AZD8055. In vitro metabolic stability study found that 3j had a comparable stability to that of AZD8055. More importantly, 3j showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.
|
Antiproliferative activity against human PC3 cells assessed as reduction in cell viability after 48 hrs by CCK8 assay
|
Homo sapiens
|
36.7
nM
|
|
Journal : Bioorg Med Chem
Title : Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity.
Year : 2018
Volume : 26
Issue : 14
First Page : 3992
Last Page : 4000
Authors : Liu Y, Xia Q, Fang L.
Abstract : Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC50 values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially 3j whose potency against SKOV3 was 8-fold higher than the positive control AZD8055. In vitro metabolic stability study found that 3j had a comparable stability to that of AZD8055. More importantly, 3j showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.
|
Antiproliferative activity against human SKOV3 cells assessed as reduction in cell viability after 48 hrs by CCK8 assay
|
Homo sapiens
|
55.0
nM
|
|
Journal : Bioorg Med Chem
Title : Design and synthesis of alkyl substituted pyridino[2,3-D]pyrimidine compounds as PI3Kα/mTOR dual inhibitors with improved pharmacokinetic properties and potent in vivo antitumor activity.
Year : 2018
Volume : 26
Issue : 14
First Page : 3992
Last Page : 4000
Authors : Liu Y, Xia Q, Fang L.
Abstract : Using pyridino[2,3-D]pyrimidine as the core, total 13 pyridino[2,3-D]pyrimidine derivatives with different alkyl substituents at C2 site have been designed and synthesized to search for novel PI3Kα/mTOR dual inhibitors. Most of the target compounds showed potent mTOR inhibition activity with IC50 values ranging from single to double digit nanomole. Five target compounds exhibited pronounced PI3Kα inhibition activity. In vitro cellular assay indicated that most of the target compounds showed excellent antiproliferative activity, especially 3j whose potency against SKOV3 was 8-fold higher than the positive control AZD8055. In vitro metabolic stability study found that 3j had a comparable stability to that of AZD8055. More importantly, 3j showed better antitumor activity and pharmacokinetic properties in vivo as compared with AZD8055.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
105.21
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Inhibition of mTORC1 (unknown origin)
|
Homo sapiens
|
0.8
nM
|
|
Journal : J Med Chem
Title : Design of Small Molecule Autophagy Modulators: A Promising Druggable Strategy.
Year : 2018
Volume : 61
Issue : 11
First Page : 4656
Last Page : 4687
Authors : He S, Li Q, Jiang X, Lu X, Feng F, Qu W, Chen Y, Sun H.
Abstract : Autophagy is a lysosome-dependent mechanism of intracellular degradation for maintaining cellular homeostasis. Dysregulation of autophagy has been verified to be closely linked to a number of human diseases. Consequently, targeting autophagy has been highlighted as a novel therapeutic strategy for clinical utility. Mounting efforts have been done in recent years to elucidate the mechanisms of autophagy regulation and to identify potential modulators of autophagy. However, most of the compounds target complex and multifaceted pathway and proteins, which may limit the evaluation of therapeutic value and in depth studies as chemical tools. Therefore, the development of specific and active autophagy modulators becomes most desirable. Here, we briefly review the regulation of autophagy and then summarize the recent development of small molecules targeting the core autophagic machinery. Finally, we put forward our viewpoints on the current problems, with the aim to provide reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective autophagy modulators.
|
Inhibition of mTORC2 (unknown origin)
|
Homo sapiens
|
2.8
nM
|
|
Journal : J Med Chem
Title : Design of Small Molecule Autophagy Modulators: A Promising Druggable Strategy.
Year : 2018
Volume : 61
Issue : 11
First Page : 4656
Last Page : 4687
Authors : He S, Li Q, Jiang X, Lu X, Feng F, Qu W, Chen Y, Sun H.
Abstract : Autophagy is a lysosome-dependent mechanism of intracellular degradation for maintaining cellular homeostasis. Dysregulation of autophagy has been verified to be closely linked to a number of human diseases. Consequently, targeting autophagy has been highlighted as a novel therapeutic strategy for clinical utility. Mounting efforts have been done in recent years to elucidate the mechanisms of autophagy regulation and to identify potential modulators of autophagy. However, most of the compounds target complex and multifaceted pathway and proteins, which may limit the evaluation of therapeutic value and in depth studies as chemical tools. Therefore, the development of specific and active autophagy modulators becomes most desirable. Here, we briefly review the regulation of autophagy and then summarize the recent development of small molecules targeting the core autophagic machinery. Finally, we put forward our viewpoints on the current problems, with the aim to provide reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective autophagy modulators.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
118.71
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
107.55
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
10.89
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
5.91
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
10.89
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
5.91
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
