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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
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26244021

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)

Approval Year

Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 23.9185 uM]
no
no
no
no
no
no
no
weak
weak
weak
weak
yes [IC50 1.6933 uM]
yes
yes
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD.
2015 Jul 15
Patents

Sample Use Guides

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
Ganetespib inhibits MG63 cell lines with IC50 of 15 nM.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:49:06 UTC 2023
Edited
by admin
on Fri Dec 15 16:49:06 UTC 2023
Record UNII
2E8412Y946
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GANETESPIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
3-(2,4-DIHYDROXY-5-ISOPROPYLPHENYL)-4-(1-METHYLINDOL-5-YL)-5-HYDROXY-4H-1,2,4-TRIAZOLE
Systematic Name English
ganetespib [INN]
Common Name English
3H-1,2,4-TRIAZOL-3-ONE, 5-(2,4-DIHYDROXY-5-(1-METHYLETHYL)PHENYL)-2,4-DIHYDRO-4-(1-METHYL-1H-INDOL-5-YL)-
Systematic Name English
5-(2,4-DIHYDROXY-5-(PROPAN-2-YL)PHENYL)-4-(1-METHYL-1H-INDOL-5-YL)-2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONE
Systematic Name English
GANETESPIB [USAN]
Common Name English
TRIAZOLONE DERIVATIVE INHIBITOR OF HEAT SHOCK PROTEIN 90
Common Name English
Ganetespib [WHO-DD]
Common Name English
STA 9090
Code English
STA-9090
Code English
Classification Tree Code System Code
NCI_THESAURUS C74526
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
Code System Code Type Description
USAN
XX-74
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
INN
9424
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
NCI_THESAURUS
C77872
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
FDA UNII
2E8412Y946
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
EPA CompTox
DTXSID401025663
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
PUBCHEM
135564985
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
CAS
888216-25-9
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
ChEMBL
CHEMBL2103879
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
DRUG BANK
DB12047
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
SMS_ID
300000034243
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
MESH
C533237
Created by admin on Fri Dec 15 16:49:06 UTC 2023 , Edited by admin on Fri Dec 15 16:49:06 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
STA-1474, a water-soluble phosphate prodrug of ganetespib
Related Record Type Details
ACTIVE MOIETY