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Details

Stereochemistry ACHIRAL
Molecular Formula C20H20N4O3
Molecular Weight 364.3978
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GANETESPIB

SMILES

CC(C)C1=CC(C2=NN=C(O)N2C3=CC4=C(C=C3)N(C)C=C4)=C(O)C=C1O

InChI

InChIKey=RVAQIUULWULRNW-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C20H20N4O3
Molecular Weight 364.3978
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Ganetespib (formerly called STA-9090) is a novel, injectable resorcinolic triazolone small molecule inhibitor of Hsp90, developed by Synta Pharmaceuticals. Ganetespib inhibits the growth of many tumor types in vitro and in vivo including AML, ALL, CML, NHL, neuroblastoma, Ewing sarcoma, rhabdoid cancer, rhabdomyosarcoma, melanoma, and carcinomas of the breast, lung, prostate, bladder and colon7-10,14-27. Ganetespib has being studied in multiple adult oncology indications. The 50% inhibitory concentrations (IC50) for Ganetespib against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. Ganetespib inhibits MG63 cell lines with IC50 of 43 nM. Ganetespib binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms' tumor 1. Ganetespib, at low nanomolar concentrations, potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. Ganetespib exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. Ganetespib has been studied in 5 completed Synta-sponsored clinical trials (Studies 9090-02, 9090-03, 9090-04, 9090-05, and 9090-07) and 3 completed Synta-sponsored studies in normal healthy volunteers (9090-12, 9090-13, and 9090-15). Ganetespib is currently being studied in 6 Synta-sponsored clinical trials. Studies include: one Phase 1 study, three Phase 2 studies, one Phase 2b study, and one Phase 3 study. Ganetespib is also being studied in 24 Investigator Sponsored Trials (ISTs)

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
15.0 nM [IC50]
5.0 nM [IC50]
5.0 nM [IC50]
51.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Ganetespib 150 mg/m2 in combination with docetaxel 75 mg/m2. On Day 1 of each 3-week treatment cycle, ganetespib and docetaxel are administered as separate 1-hour intravenous infusions. Ganetespib 150 mg/m2 is administered again on Day 15 of each cycle.
Route of Administration: Intravenous
In Vitro Use Guide
Ganetespib inhibits MG63 cell lines with IC50 of 15 nM.
Substance Class Chemical
Record UNII
2E8412Y946
Record Status Validated (UNII)
Record Version