|
Inhibition of human recombinant His6-tagged PI3K p110beta expressed in baculovirus infected cells using DiC8-PI(4,5)P2 as substrate after 20 mins by AlphaScreen assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance.
Year : 2012
Volume : 22
Issue : 21
First Page : 6671
Last Page : 6676
Authors : Giordanetto F, Wållberg A, Ghosal S, Iliefski T, Cassel J, Yuan ZQ, von Wachenfeldt H, Andersen SM, Inghardt T, Tunek A, Nylander S.
Abstract : Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favourable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Additionally, due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.
|
Inhibition of human recombinant His6-tagged PI3K p110alpha expressed in baculovirus infected cells using DiC8-PI(4,5)P2 as substrate after 20 mins by AlphaScreen assay
|
Homo sapiens
|
870.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance.
Year : 2012
Volume : 22
Issue : 21
First Page : 6671
Last Page : 6676
Authors : Giordanetto F, Wållberg A, Ghosal S, Iliefski T, Cassel J, Yuan ZQ, von Wachenfeldt H, Andersen SM, Inghardt T, Tunek A, Nylander S.
Abstract : Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favourable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Additionally, due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.
|
SANGER: Inhibition of human NCI-H2052 cell growth in a cell viability assay.
|
Homo sapiens
|
915.25
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NCI-H2342 cell growth in a cell viability assay.
|
Homo sapiens
|
842.94
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
|
727.88
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OS-RC-2 cell growth in a cell viability assay.
|
Homo sapiens
|
623.88
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human OVCAR-3 cell growth in a cell viability assay.
|
Homo sapiens
|
679.46
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human RPMI-6666 cell growth in a cell viability assay.
|
Homo sapiens
|
643.79
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
|
738.06
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
|
11.54
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SCC-9 cell growth in a cell viability assay.
|
Homo sapiens
|
857.7
nM
|
|
SANGER: Inhibition of human SCC-9 cell growth in a cell viability assay.
|
Homo sapiens
|
903.56
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
|
789.67
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SU-DHL-1 cell growth in a cell viability assay.
|
Homo sapiens
|
568.13
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
|
529.2
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human SW1783 cell growth in a cell viability assay.
|
Homo sapiens
|
305.83
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
|
35.84
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
|
532.7
nM
|
|
SANGER: Inhibition of human T47D cell growth in a cell viability assay.
|
Homo sapiens
|
937.97
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
|
995.05
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human A498 cell growth in a cell viability assay.
|
Homo sapiens
|
117.95
nM
|
|
SANGER: Inhibition of human A498 cell growth in a cell viability assay.
|
Homo sapiens
|
459.35
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BB49-HNC cell growth in a cell viability assay.
|
Homo sapiens
|
729.79
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human BT-20 cell growth in a cell viability assay.
|
Homo sapiens
|
592.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human U031 cell growth in a cell viability assay.
|
Homo sapiens
|
150.75
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
|
148.98
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human YT cell growth in a cell viability assay.
|
Homo sapiens
|
120.66
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
|
812.86
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human EW-7 cell growth in a cell viability assay.
|
Homo sapiens
|
863.56
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
|
461.61
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
|
962.22
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human J82 cell growth in a cell viability assay.
|
Homo sapiens
|
477.79
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human KURAMOCHI cell growth in a cell viability assay.
|
Homo sapiens
|
105.1
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human LB996-RCC cell growth in a cell viability assay.
|
Homo sapiens
|
498.58
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
|
17.91
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human MDA-MB-415 cell growth in a cell viability assay.
|
Homo sapiens
|
167.32
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
SANGER: Inhibition of human NALM-6 cell growth in a cell viability assay.
|
Homo sapiens
|
704.65
nM
|
|
Title : Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute
|
Inhibition of PI3Kbeta in human MAD-MB-468 cells assessed as inhibition of Ser473 Akt phosphorylation by cellular potency assay
|
Homo sapiens
|
40.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-anilinoethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours.
Year : 2014
Volume : 24
Issue : 16
First Page : 3928
Last Page : 3935
Authors : Barlaam B, Cosulich S, Degorce S, Fitzek M, Giordanetto F, Green S, Inghardt T, Hennequin L, Hancox U, Lambert-van der Brempt C, Morgentin R, Pass S, Plé P, Saleh T, Ward L.
Abstract : Starting from TGX-221, we designed a series of 9-(1-anilinoethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as potent and selective PI3Kβ/δ inhibitors. Structure-activity relationships and structure-property relationships around the aniline and the amide substituents are discussed. We identified compounds 17 and 18, which showed profound pharmacodynamic modulation of phosphorylated Akt in the PC3 prostate tumour xenograft, after a single oral dose. Compound 17 also gave significant inhibition of tumour growth in the PC3 prostate tumour xenograft model after chronic oral dosing.
|
Inhibition of human recombinant PI3Kbeta assessed as PIP3 production by AlphaScreen assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.
Year : 2014
Volume : 24
Issue : 16
First Page : 3936
Last Page : 3943
Authors : Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T.
Abstract : Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
|
Inhibition of human recombinant PI3Kalpha assessed as PIP3 production by AlphaScreen assay
|
Homo sapiens
|
870.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.
Year : 2014
Volume : 24
Issue : 16
First Page : 3936
Last Page : 3943
Authors : Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T.
Abstract : Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
|
Inhibition of human recombinant PI3Kdelta assessed as PIP3 production by AlphaScreen assay
|
Homo sapiens
|
80.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.
Year : 2014
Volume : 24
Issue : 16
First Page : 3936
Last Page : 3943
Authors : Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T.
Abstract : Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
|
Antiplatelet activity against human platelet assessed as inhibition of collagen-induced platelet rich plasma aggregation by light transmission aggregometry
|
Homo sapiens
|
280.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.
Year : 2014
Volume : 24
Issue : 16
First Page : 3936
Last Page : 3943
Authors : Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T.
Abstract : Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
|
Antiplatelet activity against human platelet assessed as inhibition of ADP-induced whole blood aggregation by light transmission aggregometry
|
Homo sapiens
|
270.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents.
Year : 2014
Volume : 24
Issue : 16
First Page : 3936
Last Page : 3943
Authors : Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T.
Abstract : Optimization of AZD6482 (2), the first antiplatelet PI3Kβ inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kβ inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
|
ATP competitive inhibition of human recombinant PI3Kbeta assessed as PIP3 production by Alpha-screen assay
|
Homo sapiens
|
10.0
nM
|
|
Journal : J Med Chem
Title : Class II Phosphoinositide 3-Kinases as Novel Drug Targets.
Year : 2017
Volume : 60
Issue : 1
First Page : 47
Last Page : 65
Authors : Falasca M, Hamilton JR, Selvadurai M, Sundaram K, Adamska A, Thompson PE.
Abstract : The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases central to regulating a wide range of important intracellular processes. Despite the vast knowledge around class I PI3Ks, the class II PI3Ks have been neglected, seemingly only due to the chronology of their discovery. Here we focus on the cellular functions of the three class II PI3K isoforms, PI3KC2α, PI3KC2β, and PI3KC2γ, in different cell systems and underline the emerging importance of these enzymes in different physiological and pathological contexts. We provide an overview on the current development of class II PI3 kinase inhibitors and outline the potential use for such inhibitors. The field is in its infancy as compared to their class I counterparts. Nevertheless, recent advances in understanding the roles of class II PI3 kinases in different pathological contexts is leading to an increased interest in the development of specific inhibitors that can provide potential novel pharmacological tools.
|
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
|
-6.35
%
|
|
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 human PIK3CB by alphascreen assay
|
Homo sapiens
|
40.0
nM
|
|
Journal : J Med Chem
Title : The Exploration of Chirality for Improved Druggability within the Human Kinome.
Year : 2020
Volume : 63
Issue : 2
First Page : 441
Last Page : 469
Authors : Saha D, Kharbanda A, Yan W, Lakkaniga NR, Frett B, Li HY.
Abstract : Chirality is important in drug discovery because stereoselective drugs can ameliorate therapeutic difficulties including adverse toxicity and poor pharmacokinetic profiles. The human kinome, a major druggable enzyme class has been exploited to treat a wide range of diseases. However, many kinase inhibitors are planar and overlap in chemical space, which leads to selectivity and toxicity issues. By exploring chirality within the kinome, a new iteration of kinase inhibitors is being developed to better utilize the three-dimensional nature of the kinase active site. Exploration into novel chemical space, in turn, will also improve drug solubility and pharmacokinetic profiles. This perspective explores the role of chirality to improve kinome druggability and will serve as a resource for pioneering kinase inhibitor development to address current therapeutic needs.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
12.3
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
14.21
%
|
|
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
|
-0.31
%
|
|
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
|
-0.28
%
|
|
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
|
-0.28
%
|
|
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
|
-0.31
%
|
|
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.
|
Inhibition of recombinant human PI3Kalpha assessed as reduction in PIP3 formation by AlphaScreen assay
|
Homo sapiens
|
80.0
nM
|
|
|
Inhibition of recombinant human PI3Kbeta assessed as reduction in PIP3 formation by AlphaScreen assay
|
Homo sapiens
|
10.0
nM
|
|
|
Inhibition of recombinant human PI3Kgamma assessed as reduction in PIP3 formation by AlphaScreen assay
|
Homo sapiens
|
870.0
nM
|
|
