ganetespib   Click here for help

GtoPdb Ligand ID: 13309

Synonyms: compound 8 [PMID: 23965125] | STA-9090 | STA9090
PDB Ligand
Compound class: Synthetic organic
Comment: Ganetespib (STA-9090) is a small molecule pan-HSP90 inhibtor [10-11]. It has pro-apoptotic and anti-proliferative actions in a range of cancer cell types [1,4-6,9,11]. Ganetespib has been proposed as a senolytic compound [2-3] that is able to promote cell death in AR-induced senescent prostate cancer cells [7].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

ganetespib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 3
Topological polar surface area 88.4
Molecular weight 364.4
XLogP 3.01
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CC(C)C1=CC(=C(C=C1O)O)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C)C=C4
Isomeric SMILES CC(C)C1=C(C=C(C(=C1)C2=NNC(=O)N2C3=CC4=C(C=C3)N(C=C4)C)O)O
InChI InChI=1S/C20H20N4O3/c1-11(2)14-9-15(18(26)10-17(14)25)19-21-22-20(27)24(19)13-4-5-16-12(8-13)6-7-23(16)3/h4-11,25-26H,1-3H3,(H,22,27)
InChI Key RVAQIUULWULRNW-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Acquaviva J, Smith DL, Sang J, Friedland JC, He S, Sequeira M, Zhang C, Wada Y, Proia DA. (2012)
Targeting KRAS-mutant non-small cell lung cancer with the Hsp90 inhibitor ganetespib.
Mol Cancer Ther, 11 (12): 2633-43. [PMID:23012248]
2. Fuhrmann-Stroissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, Grassi D, Gregg SQ, Stripay JL, Dorronsoro A et al.. (2017)
Identification of HSP90 inhibitors as a novel class of senolytics.
Nat Commun, 8 (1): 422. [PMID:28871086]
3. Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD. (2018)
Hsp90 inhibitors as senolytic drugs to extend healthy aging.
Cell Cycle, 17 (9): 1048-1055. [PMID:29886783]
4. He S, Zhang C, Shafi AA, Sequeira M, Acquaviva J, Friedland JC, Sang J, Smith DL, Weigel NL, Wada Y et al.. (2013)
Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression.
Int J Oncol, 42 (1): 35-43. [PMID:23152004]
5. Proia DA, Foley KP, Korbut T, Sang J, Smith D, Bates RC, Liu Y, Rosenberg AF, Zhou D, Koya K et al.. (2011)
Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling.
PLoS One, 6 (4): e18552. [PMID:21533169]
6. Proia DA, Sang J, He S, Smith DL, Sequeira M, Zhang C, Liu Y, Ye S, Zhou D, Blackman RK et al.. (2012)
Synergistic activity of the Hsp90 inhibitor ganetespib with taxanes in non-small cell lung cancer models.
Invest New Drugs, 30 (6): 2201-9. [PMID:22227828]
7. Pungsrinont T, Sutter MF, Ertingshausen MCCM, Lakshmana G, Kokal M, Khan AS, Baniahmad A. (2020)
Senolytic compounds control a distinct fate of androgen receptor agonist- and antagonist-induced cellular senescent LNCaP prostate cancer cells.
Cell Biosci, 10: 59. [PMID:32351687]
8. Schuetz DA, de Witte WEA, Wong YC, Knasmueller B, Richter L, Kokh DB, Sadiq K, Bosma R, Nederpelt I, Heitman LH et al.. 
K4DD drug target binding kinetics data.
,. DOI: 10.6019/CHEMBL3885741
9. Shimamura T, Perera SA, Foley KP, Sang J, Rodig SJ, Inoue T, Chen L, Li D, Carretero J, Li YC et al.. (2012)
Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer.
Clin Cancer Res, 18 (18): 4973-85. [PMID:22806877]
10. Taldone T, Patel PD, Patel M, Patel HJ, Evans CE, Rodina A, Ochiana S, Shah SK, Uddin M, Gewirth D et al.. (2013)
Experimental and structural testing module to analyze paralogue-specificity and affinity in the Hsp90 inhibitors series.
J Med Chem, 56 (17): 6803-18. [PMID:23965125]
11. Ying W, Du Z, Sun L, Foley KP, Proia DA, Blackman RK, Zhou D, Inoue T, Tatsuta N, Sang J et al.. (2012)
Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy.
Mol Cancer Ther, 11 (2): 475-84. [PMID:22144665]