Other drug agents
MedKoo product information:
Description of Ganetespib: Ganetespib (STA-9090) is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor STA-9090 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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).
Current developer: Synta Pharmaceuticals Corp., USA
According to Synta's website, STA-9090 is a novel, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90), being developed for treating multiple solid tumor and hematologic cancers. STA-9090 was discovered and developed internally at Synta and has a chemical structure unrelated to the first-generation, ansamycin family of Hsp90 inhibitors such as 17-AAG. In preclinical studies, STA-9090 has shown potency up to 100 times greater than the first-generation Hsp90 inhibitors as well as activity against a wider range of kinases. In in vitro and in vivo models, STA-9090 has shown potent activity against a wide range of cancer types, including lung, prostate, colon, breast, gastric, pancreatic, melanoma and certain hematologic cancers - as well as potent activity against cancers resistant to Gleevec, Sutent, Tarceva, Sprycel, and 17-AAG.
Highlight of recent study using Ganespib (STA-9090)
Ganetespib (STA-9090) in Cancer Cells with Activated JAK/STAT Signaling (published in 2011) ganetespib exhibits potent in vitro and in vivo activity in a range of solid and hematological tumor cells that are dependent on JAK2 activity for growth and survival. Of note, ganetespib treatment results in sustained depletion of JAK2, including the constitutively active JAK2V617F mutant, with subsequent loss of STAT activity and reduced STAT-target gene expression. (source: PLoS One. 2011 Apr 14;6(4):e18552.)
Kaplan-Meier analysis of overall survival in a leukemia model established by i.v. injection of HEL92.1.7 cells into SCID mice, which resulted in the development of disseminated disease. Beginning one day after tumor cell implantation, ganetespib was i.v. dosed at its HNSTD (25 mg/kg) on a five-times per week schedule for 3 weeks through day 19 (n = 10/group). *P,0.0001; 2-sided log-rank test. (source: PLoS One. 2011 Apr 14;6(4):e18552.)
SCID mice were subcutaneously implanted with MV4-11 acute myeloid leukemia cells. Mice bearing established MV4-11 xenografts (100200 mm3, n = 8 mice/group) were i.v. dosed (arrowheads) with ganetespib at either 25 or 150 mg/kg once weekly for 3 weeks, or at the HNSTD of 25 mg/kg five-times per week, as indicated. % T/C values are indicated to the right of each growth curve and the error bars are the s.e.m. (source: PLoS One. 2011 Apr 14;6(4):e18552.)
Phase II trial result: Ganetespib showed clinical activity on patients with Non-small Cell Lung Cancer (published in 2011): According to Synta Pharmaceuticals Corp's new release (Jul 7, 2011), Ganetespib has shown encouraging single agent clinical activity and a good safety profile in pretreated advanced NSCLC patients, said Julie Brahmer, M.D., Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital. The case study presented today shows a patient whose ALK positive cancer had progressed on treatment with crizotinib, the most clinically advanced ALK inhibitor, who then experienced significant tumor shrinkage within the first several weeks of treatment with ganetespib. The results for ganetespib in NSCLC, particularly in patients with ALK or KRAS mutations, suggest this compound has promising potential to benefit lung cancer patients. Of the 23 patients in the Phase 2 trial tested for ALK translocation or rearrangement (ALK+), eight patients were ALK+ in at least one assay. Six of these eight patients (75%) showed tumor shrinkage in target lesions, one patient showed no change in tumor size, and one patient achieved stable disease (tumor growth <20%). The disease control rate in this population was 7/8 (88%), and the objective response rate (CR+PR) was 4/8 (50%).
Phase I trial result: Ganetespib Shows Clinical Activity
in HER2+ and Triple Negative Metastatic Breast Cancer
(published in 2011). According to
Synat's new release (
Phase I trial result: Ganetespib Shows Clinical Activity in HER2+ and Triple Negative Metastatic Breast Cancer (published in 2011).
According to Synat's new release (December 08, 2011), "The single agent ganetespib results presented today further validates Hsp90 as a target for treating HER2-positive breast cancer and suggest Hsp90 inhibition may be an important new approach to treating triple negative breast cancer, said Shanu Modi, M.D., Memorial Sloan-Kettering Cancer Center, the principal investigator on this study. 15% (2/13) of the patients with the HER2 gene amplification experienced a partial response in this trial and an additional 46% (6/13) achieved stable disease. These encouraging results for Hsp90 inhibition in HER2 positive disease are consistent with results from an earlier Phase 2 study of 17-AAG, a first generation Hsp90 inhibitor, in which 22% (6/27) achieved partial response and an additional 37% (10/27) achieved stable disease1. While in the prior study 17-AAG was given in combination with trastuzumab, in the current study ganetespib was given as a monotherapy. Together, these studies present compelling evidence that Hsp90 inhibition is effective in HER2-positive breast cancer.
1. Cancer therapy using a combination of a heat-shock
protein 90 inhibitory compound and a vascular endothelial growth factor
receptor inhibitor By Blackman, Ronald K.; Foley, Kevin P.; Proia, David
From PCT Int. Appl. (2011), WO 2011133521 A2 20111027.
(Keyword; CAS#; MedKoo code#)
About us | Services | Products | News | Careers | Contact us