Ganetespib

Description

Ganetespib (888216-25-9) is an inhibitor of heat shock protein 90 (IC50 = 19 nM, canine C2 malignant mast cells; 4 nM, canine BR malignant mast cells) binding to the N-terminal ATP site.1? It displayed potent cytotoxicity against a panel of 57 transformed cell lines of both hematologic and solid tumors? with IC50’s between 14 and 280 nM.2 Ganetespib enhanced T-cell-mediated killing of human melanoma cells and potentiated responses to anti-CTLA4 and anti-PD1 therapy via upregulation of interferon response genes.3 In multiple clinical trials for various cancers.

What are the applications of Application

Ganetespib is a unique triazolone-containing Hsp90 inhibitor with an IC50 of 4 nM for OSA 8 cells

Definition

ChEBI: Ganetespib is a member of triazoles and a ring assembly. It is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity.

General Description

A synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Ganetespib binds to and inhibits Hsp90, resulting in the proteasomal degradation of oncogenic client proteins, the inhibition of cell proliferation and the elevation of heat shock protein 72 (Hsp72); it may inhibit the activity of multiple kinases, such as c-Kit, EGFR, and Bcr-Abl, which as client proteins depend on functional HsP90 for maintenance. Hsp90, a 90 kDa molecular chaperone upregulated in a variety of tumor cells, plays a key role in the conformational maturation, stability and function of "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.

References

Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non–Small Cell Lung Cancer DOI:10.1158/1078-0432.CCR-11-2967
https://www.cancer.gov/publications/dictionaries/cancer-drug/def/ganetespib
Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy DOI: 10.1158/1535-7163.MCT-11-0755
Role of Ganetespib, an HSP90 Inhibitor, in Cancer Therapy: From Molecular Mechanisms to Clinical Practice doi: 10.3390/ijms24055014
A first in human, safety, pharmacokinetics, and clinical activity phase I study of once weekly administration of the Hsp90 inhibitor ganetespib (STA-9090) in patients with solid malignancies DOI:10.1186/1471-2407-13-152
Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner DOI:10.1038/cddis.2017.108