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
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)
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/26244021
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)
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL614347 |
15.0 nM [IC50] | ||
5.0 nM [IC50] | |||
Target ID: CHEMBL4303 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965125 |
5.0 nM [IC50] | ||
Target ID: CHEMBL1075132 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23965125 |
51.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes | ||||
yes |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01348126
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19544563
Ganetespib inhibits MG63 cell lines with IC50 of 15 nM.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C74526
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
XX-74
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
9424
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
C77872
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
2E8412Y946
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
DTXSID401025663
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
135564985
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
888216-25-9
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
CHEMBL2103879
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
DB12047
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
300000034243
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY | |||
|
C533237
Created by
admin on Fri Dec 15 16:49:06 GMT 2023 , Edited by admin on Fri Dec 15 16:49:06 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)