ALVESPIMYCIN

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Synonyms
Status
Molecule Category Free-form
UNII 001L2FE0M3

Structure

InChI Key KUFRQPKVAWMTJO-LMZWQJSESA-N
Smiles CO[C@H]1/C=C\C=C(/C)C(=O)NC2=CC(=O)C(NCCN(C)C)=C(C[C@@H](C)C[C@H](OC)[C@H](O)[C@@H](C)/C=C(\C)[C@@H]1OC(N)=O)C2=O
InChI
InChI=1S/C32H48N4O8/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40)/b11-9-,19-10+,21-16+/t18-,20+,25+,26+,28-,30+/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C32H48N4O8
Molecular Weight 616.76
AlogP 1.91
Hydrogen Bond Acceptor 10.0
Hydrogen Bond Donor 4.0
Number of Rotational Bond 7.0
Polar Surface Area 169.52
Molecular species NEUTRAL
Aromatic Rings 0.0
Heavy Atoms 44.0

Bioactivity

Mechanism of Action Action Reference
Heat shock protein HSP90 inhibitor INHIBITOR PubMed
Protein: Heat shock protein HSP90
Description: Heat shock protein HSP 90-alpha
Organism : Homo sapiens
P07900 ENSG00000080824
Protein: Heat shock protein HSP90
Description: Heat shock protein HSP 90-beta
Organism : Homo sapiens
P08238 ENSG00000096384
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Other cytosolic protein
4-62 5-100 87-500 680 88
Other membrane protein
65 - - - -
Transcription factor
- 4-61 - - -
Assay Description Organism Bioactivity Reference
Binding affinity for human heat shock protein 90 in scintillation proximity assay Homo sapiens 500.0 nM
Cytotoxicity against SKBr3 cells Homo sapiens 24.0 nM
Inhibition of BODIPY-AG binding to human HSP90 Homo sapiens 62.0 nM
Inhibition of BODIPY-AG binding to dog Grp94 Canis lupus familiaris 65.0 nM
Degradation of Her2 in SKBR3 cells Homo sapiens 8.0 nM
Degradation of Her2 in SKOV3 cells Homo sapiens 46.0 nM
Upregulation of Hsp70 in SKBR3 cells Homo sapiens 4.0 nM
Upregulation of Hsp70 in SKOV3 cells Homo sapiens 14.0 nM
Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay Homo sapiens 36.0 nM
Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay Homo sapiens 61.0 nM
Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gene assay Homo sapiens 3.6 nM
Inhibition of TNF-alpha-induced NF-kappaB activation in human HeLa cells Homo sapiens 150.0 nM
Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation Homo sapiens 17.6 nM
Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation Homo sapiens 4.5 nM
Cytotoxicity against human MDA-MB-231 cells by MTT assay Homo sapiens 5.8 nM
Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation Homo sapiens 24.3 nM
Cytotoxicity against human A2058 cells by MTT assay Homo sapiens 2.1 nM
Inhibition of Hsp90 in human A2058 cells Homo sapiens 7.9 nM
Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay Homo sapiens 24.0 nM
Binding affinity to human recombinant HSP90 Homo sapiens 500.0 nM
Cytotoxicity against human MCF7 cells after 72 hrs by celltiter-glo assay Homo sapiens 230.0 nM
Cytotoxicity against human SKOV3 cells after 72 hrs by celltiter-glo assay Homo sapiens 220.0 nM
Cytotoxicity against human A549 cells after 72 hrs by celltiter-glo assay Homo sapiens 68.0 nM
Cytotoxicity against human CCRF-CEM cells after 72 hrs by celltiter-96 aqueous one solution assay Homo sapiens 540.0 nM
Cytotoxicity against human MCF7 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol Homo sapiens 862.0 nM
Cytotoxicity against human SKBR3 cells after 72 hrs in presence of NQO1 inhibitor dicoumarol Homo sapiens 230.0 nM
Binding affinity to human recombinant Hsp90alpha N-terminal domain by scintillation proximity assay Homo sapiens 500.0 nM
Binding affinity to human recombinant Hsp90alpha N-terminal domain by isothermal titration calorimetry Homo sapiens 87.0 nM
Cytotoxicity against human SKBR3 cells after 72 hrs Homo sapiens 58.0 nM
Cytotoxicity against human SKOV3 cells after 72 hrs Homo sapiens 122.0 nM
Cytotoxicity against human HCT116 cells after 72 hrs Homo sapiens 57.0 nM
Cytotoxicity against human MCF7 cells after 72 hrs Homo sapiens 71.0 nM
Binding affinity to Hsp90 in human SKBR3 cells Homo sapiens 24.0 nM
Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis Homo sapiens 57.2 nM
Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA Homo sapiens 79.5 nM
Displacement of [3H]pGA from His-tagged Hsp90 by scintillation proximity assay None 250.0 nM
Inhibition of Hsp90 in human H1299 assessed as degradation of Hsp90 client protein Akt Homo sapiens 100.0 nM
Inhibition of hypoxia-induced HIF1alpha protein accumulation in human Hep3B cells treated for 30 mins measured after 12 hrs by Western blot analysis Homo sapiens 57.0 nM
Inhibition of hypoxia-induced VEGF protein secretion in human Hep3B cells after 16 hrs by ELISA Homo sapiens 79.0 nM
Binding affinity to Hsp90 N-terminal ATPase domain by isothermal titration calorimetry assay None 210.0 nM
Cytotoxicity against human HCT116 cells by Alamar blue assay Homo sapiens 50.0 nM
Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days selected with 40 nM HCV-796 and 800 nM boceprevir by qRT-PCR analysis Hepatitis C virus 3.1 nM
Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human HuH7 cells assessed as GAPDH RNA or 18S rRNA level after 3 days by qRT-PCR analysis Hepatitis C virus 1.2 nM
Inhibition of human HSP90 in human NCI-H1299 cells assessed as Akt degradation after 24 hrs by luminex assay Homo sapiens 100.0 nM
Displacement of [3H]-(R)-2-(5-chloro-2,4-dihydroxybenzoyl)-N-ethylisoindoline-1-carboxamide from human his(6)-tagged HSP90alpha after 30 mins by scintillation proximity assay Homo sapiens 680.0 nM
Inhibition of Hsp90 in human COLO205 cells xenografted in mouse assessed as Raf1 degradation at 100 mg/kg administered QD for 2 days measured 8 hrs post-last dose Mus musculus 84.0 %
Antiproliferative activity against human HCT116 cells assessed as inhibition of cell viability after 48 hrs by MTT assay Homo sapiens 780.0 nM
Antiproliferative activity against human MCF7 cells assessed as inhibition of cell viability after 48 hrs by MTT assay Homo sapiens 390.0 nM
Inhibition of full-length Hsp90-ATPase activity (unknown origin) assessed as inhibition of ATP hydrolysis by spectrophotometry Homo sapiens 930.0 nM
Inhibition of HSP90 (unknown origin)-mediated ATPase activity at 40 uM after 3 hrs by malachite green assay relative to control Homo sapiens 88.31 %
Displacement of FITC-geldanamycin from HSP90 (unknown origin) after 30 mins by fluorescence polarization assay Homo sapiens 90.0 nM
Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay Homo sapiens 800.0 nM
Antiproliferative activity against human A231 cells after 48 hrs by MTT assay Homo sapiens 170.0 nM
Drug metabolism in human liver microsomes assessed as 1 uM CYP3A inhibitor ketoconazole-mediated inhibition of (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-(dimethylamino)ethylamino)-13-hydroxy-10-(hydroxymethyl)-8,14-dimethoxy-4,12,16-trimethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate formation at 1 uM 17-DMAG by liquid chromatography-tandem mass spectrometry Homo sapiens 75.0 %
Drug metabolism in human liver microsomes assessed as 1 uM CYP3A inhibitor ketoconazole-mediated inhibition of (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-(dimethylamino)-1-hydroxyethylamino)-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate formation at 1 uM 17-DMAG by liquid chromatography-tandem mass spectrometry Homo sapiens 77.0 %
Drug metabolism in human liver microsomes assessed as 1 uM CYP3A inhibitor ketoconazole-mediated inhibition of (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-(dimethylamino)ethylamino)-13,14-dihydroxy-8-methoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate formation at 1 uM 17-DMAG by liquid chromatography-tandem mass spectrometry Homo sapiens 79.0 %
Drug metabolism in human liver microsomes assessed as 1 uM CYP3A inhibitor ketoconazole-mediated inhibition of (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-(2-(dimethylamino)ethylamino)-8,13-dihydroxy-14-methoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate formation at 1 uM 17-DMAG by liquid chromatography-tandem mass spectrometry Homo sapiens 81.0 %
Drug metabolism in human liver microsomes assessed as 1 uM CYP3A inhibitor ketoconazole-mediated inhibition of (4E,6Z,8S,9S,10E,12R,13R,14S,16R)-19-(2-(dimethylamino)-1-hydroxyethylamino)-13-hydroxy-12,16-bis(hydroxymethyl)-8,14-dimethoxy-4,10-dimethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl carbamate formation at 1 uM 17-DMAG by liquid chromatography-tandem mass spectrometry Homo sapiens 83.0 %
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 -0.7 %
Inhibition of Hsp90 in human SKBR3 cells Homo sapiens 24.0 nM
Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as inhibition of cell growth after 72 hrs by MTT assay Homo sapiens 10.0 nM
Cytotoxicity against HGF-induced erlotinib-resistant human Ma1 cells assessed as inhibition of cell growth after 72 hrs by MTT assay Homo sapiens 10.0 nM
Inhibition of 6x-His tagged human recombinant full length Hsp90alpha ATPase preincubated for 0.5 hrs followed by ATP addition measured after 30 mins by HTRF assay Homo sapiens 919.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 12.91 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 10.6 %
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 -0.32 % 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 -0.33 % 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 -0.33 % 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 -0.32 %

Related Entries

Cross References

Resources Reference
ChEBI 65324
ChEMBL CHEMBL383824
DrugBank DB12442
FDA SRS 001L2FE0M3
Guide to Pharmacology 9828
PDB KOS
PubChem 5288674
SureChEMBL SCHEMBL5449716
ZINC ZINC000100030312
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