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Compound Detail

CHEMBL383824

ALVESPIMYCIN
🧪 Phase II
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🧪 Phase II
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

Basic Information

ChEMBL ID CHEMBL383824
Name ALVESPIMYCIN
Phase Phase II
Structure Type MOL
InChI Key KUFRQPKVAWMTJO-LMZWQJSESA-N

Known Names

Alvespimicina Alvespimycin Alvespimycine NSC-707545
29
Targets
74
Activities
4
Assay Types
4
PK Parameters
20
Publications
4
Known Names
1
Indications
2
Mechanisms

Molecular Properties

616.8
MW (Da)
1.91
ALogP
10
HBA
4
HBD
169.5
PSA (Ų)
0.24
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Flags

Natural Product
USAN Stem -mycin
USAN Year 2008

Extended Properties

Molecular Formula C32H48N4O8
MW 616.76
Aromatic Rings 0
Heavy Atoms 44
NP-Likeness 2.12

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Heat shock protein HSP90 inhibitor INHIBITOR Heat shock protein HSP90
Reactive oxygen species - -

Indications

Breast Neoplasms

Activity Summary

IC50 57 meas. best 8.68
EC50 10 meas. best 8.92
Kd 5 meas. best 7.06
Ki 2 meas. best 6.6

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Hepatitis C virus
CHEMBL379
EC50 8.92 8.715 1.2 2
A2058
CHEMBL613503
IC50 8.68 8.68 2.1 1
Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha
CHEMBL2221345
IC50 8.44 7.6967 3.6 3
Heat shock protein HSP90
CHEMBL2095165
EC50 8.4 7.8333 4.0 6
Heat shock protein HSP90
CHEMBL2095165
IC50 8.35 7.555 4.5 6
MDA-MB-231
CHEMBL400
IC50 8.24 6.29 5.8 2
Hs-578T
CHEMBL614645
IC50 8.08 8.08 8.4 1
PC-9
CHEMBL614102
IC50 8.0 8.0 10.0 1
Unchecked
CHEMBL612545
IC50 8.0 7.41 10.0 2
SK-BR-3
CHEMBL613834
IC50 7.62 7.28 24.0 4
Heat shock protein HSP 90-beta
CHEMBL4303
IC50 7.62 6.6375 24.0 4
HCT-116
CHEMBL394
IC50 7.3 6.6425 50.0 4
Hypoxia-inducible factor 1-alpha
CHEMBL4261
IC50 7.24 7.24 57.0 2
NCI-N87
CHEMBL614197
EC50 7.21 7.21 62.0 1
Endoplasmin
CHEMBL4748
EC50 7.19 7.19 65.0 1
A549
CHEMBL392
IC50 7.17 7.17 68.0 1
MCF7
CHEMBL387
IC50 7.15 6.4433 71.0 6
Hep 3B2
CHEMBL4296437
IC50 7.1 7.1 79.0 2
Heat shock protein HSP 90-alpha
CHEMBL3880
Kd 7.06 6.5533 87.0 3
SK-OV-3
CHEMBL614925
IC50 6.91 6.785 122.0 2
Lysine-specific demethylase 5A
CHEMBL2424504
IC50 6.89 6.89 130.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.77 5.9875 170.0 4
Unchecked
CHEMBL612545
Kd 6.68 6.68 210.0 1
Unchecked
CHEMBL612545
Ki 6.6 6.6 250.0 1
Lysine-specific demethylase 6B
CHEMBL1938211
IC50 6.4 6.4 400.0 1
Heat shock protein HSP 90-beta
CHEMBL4303
Kd 6.3 6.3 500.0 1
CCRF-CEM
CHEMBL382
IC50 6.27 5.935 540.0 2
Heat shock protein HSP 90-alpha
CHEMBL3880
Ki 6.17 6.17 680.0 1
Lysine-specific demethylase 4B
CHEMBL3313832
IC50 6.16 6.16 700.0 1
Lysine-specific demethylase 4C
CHEMBL6175
IC50 6.16 6.16 700.0 1
Heat shock protein HSP 90-alpha
CHEMBL3880
IC50 6.04 6.04 919.0 1
NCI-H596
CHEMBL612256
IC50 5.96 5.96 1100.0 1
HeLa
CHEMBL399
IC50 5.69 5.69 2060.0 1
AGS
CHEMBL613860
IC50 4.8 4.8 16000.0 2
BT-549
CHEMBL614072
IC50 4.77 4.77 17100.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 12.3 mL.min-1.g-1 Homo sapiens
CL 7.4 L/hr Homo sapiens
T1/2 0.4333 hr -
T1/2 16.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Hepatitis C virus EC50 = 1.2 nM 8.92 Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human ... 18936191
A2058 IC50 = 2.1 nM 8.68 Cytotoxicity against human A2058 cells by MTT assay 18929486
Hepatitis C virus EC50 = 3.1 nM 8.51 Antiviral activity against Hepatitis C virus genotype 1b Con1 infected in human ... 18936191
Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha IC50 = 3.6 nM 8.44 Inhibition of hypoxia-induced HIF1 activation in human AGS cells by reporter gen... 18359631
Heat shock protein HSP90 EC50 = 4.0 nM 8.4 Upregulation of Hsp70 in SKBR3 cells 16854066
Heat shock protein HSP90 IC50 = 4.5 nM 8.35 Inhibition of Hsp90 in human MDA-MB-231 cells assessed as her2 degradation 18929486
MDA-MB-231 IC50 = 5.8 nM 8.24 Cytotoxicity against human MDA-MB-231 cells by MTT assay 18929486
Heat shock protein HSP90 EC50 = 7.9 nM 8.1 Inhibition of Hsp90 in human A2058 cells 18929486
Heat shock protein HSP90 EC50 = 8.0 nM 8.1 Degradation of Her2 in SKBR3 cells 16854066
Hs-578T IC50 = 8.4 nM 8.08 Anticancer activity against human Hs-578T cells assessed as cell growth inhibiti... 33650861
Unchecked IC50 = 10.0 nM 8.0 Cytotoxicity against HGF-induced erlotinib-resistant human Ma1 cells assessed as... 26844689
PC-9 IC50 = 10.0 nM 8.0 Cytotoxicity against HGF-induced erlotinib-resistant human PC9 cells assessed as... 26844689
Heat shock protein HSP90 EC50 = 14.0 nM 7.85 Upregulation of Hsp70 in SKOV3 cells 16854066
Heat shock protein HSP90 IC50 = 17.6 nM 7.75 Inhibition of Hsp90 in human MDA-MB-231 cells assessed as Akt degradation 18929486
Heat shock protein HSP 90-beta IC50 = 24.0 nM 7.62 Binding affinity to Hsp90 in human SKBR3 cells 19017562
SK-BR-3 IC50 = 24.0 nM 7.62 Cytotoxicity against SKBr3 cells 16165354
SK-BR-3 IC50 = 24.0 nM 7.62 Cytotoxicity against human SKBR3 cells after 72 hrs by celltiter-glo assay 19405528
Heat shock protein HSP90 IC50 = 24.0 nM 7.62 Inhibition of Hsp90 in human SKBR3 cells 26844689
Heat shock protein HSP90 IC50 = 24.3 nM 7.61 Inhibition of Hsp90 in human A2058 cells assessed as Akt degradation 18929486
Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha IC50 = 36.0 nM 7.44 Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypox... 17583950

Literature References

PubMed DOI Target Context # Activities
21177985 10.1124/dmd.110.036418 Liver microsome 14
28816449 10.1021/acs.jmedchem.7b00978 Heat shock protein HSP90 6
21177985 10.1124/dmd.110.036418 Cytochrome P450 3A5 5
16854066 10.1021/jm0603116 Heat shock protein HSP90 5
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
18929486 10.1016/j.bmcl.2008.09.081 Heat shock protein HSP90 4
39042910 10.1021/acs.jmedchem.4c00932 Unchecked 3
24763261 10.1016/j.ejmech.2014.03.061 Heat shock protein HSP 90-beta 3
18936191 10.1128/aac.01081-08 Hepatitis C virus 3
19405528 10.1021/jm900098v CCRF-CEM 2
17603540 10.1038/nchembio.2007.10 Heat shock protein HSP 90-beta 2
19231864 10.1021/jm900012a Heat shock protein HSP 90-alpha 2
21177985 10.1124/dmd.110.036418 Homo sapiens 2
19231864 10.1021/jm900012a SK-BR-3 2
22877636 10.1016/j.bmcl.2012.07.052 Mus musculus 2
24763261 10.1016/j.ejmech.2014.03.061 NON-PROTEIN TARGET 2
- 10.6019/CHEMBL4808148 Histone deacetylase 6 2
19231864 10.1021/jm900012a MCF7 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
17583950 10.1021/np060482d Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha 2

Data from ChEMBL 36 via Core Engine