Significant degradation of ALK was observed after exposure to the Hsp90 inhibitor ganetespib (Synta Pharmaceuticals) in cells transfected with EML4-ALK variants 1 or 2 but not variants 3a or 5a (Fig. Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. Phase 3. We do not sell to … The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. PubMed PMID: 28167505; PMCID: PMC5418121. Ganetespib is the clinically most advanced Hsp90 inhibitor which has been applied in more than 1,600 individuals (patients and healthy volunteers) throughout Phase I-III studies. Ganetespib demonstrated potent in vitro cytotoxic activity (median rIC 50 8.8nM, range 4.4-27.1nM). Pharmacologic inhibition of histone We identified heat shock protein 90 (HSP90) inhibitors amongst the top compounds that improved T cell mediated cytotoxicity of treated tumor cells. It binds to the ATP pocket in the N-terminus of Hsp90, resulting in down-regulation of Hsp90 client protein levels. Ganetespib, an Hsp90 inhibitor, was tested against the PPTP in vitro cell line panel and selected xenografts in vivo, including JAK2- and BRAF-mutated models. An Hsp90 inhibitor is a substance that inhibits that activity of the Hsp90 heat shock protein.Since Hsp90 stabilizes a variety of proteins required for survival of cancer cells, these substances may have therapeutic benefit in the treatment of various types of malignancies. For ganetespib, the dosage was 200 mg/m 2 on days 1, 8 and 15 of a 28-day cycle. Nihal Ahmad. Acquired resistance to the Hsp90 inhibitor, ganetespib, in KRAS-mutant NSCLC is mediated via reactivation of the ERK-p90RSK-mTOR signaling network. Ganetespib is a unique resorcinolic triazolone small molecule inhibitor of Hsp90, structurally unrelated to the ansamycin class, which exhibits potent activity in a broad range of preclinical models of human malignancies (26,41). Ganetespib (STA-9090) is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. In this manner, Hsp90 inhibition by ganetespib can be viewed as a multi-nodal modality rather than a target-specific Discussion therapeutic approach, such as that engendered by a JAK2 or other Persistent JAK/STAT activation is oncogenic and characteristic kinase inhibitor (Figure 7). The HSP90 inhibitor ganetespib potentiates the antitumor efficacy of PD-L1 antibody treatment in syngeneic mouse tumor models. The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of 177 Lu-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. 888216-25-9 Ganetespib is a potent, synthetic, small molecule inhibitor of Hsp90, a chaperone protein that is essential to the function of certain other proteins that drive the growth, proliferation, and survival of many different types of cancer. 37 Full PDFs related to this paper. HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma In conclusion, our data support that the HSP90 inhibitor, STA-9090, suppresses the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. Ganetespib (formerly STA-9090) is a potent, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90). Hsp90 is overexpressed in cancer cells and may help to stabilize less stable proteins produced by DNA mutations. Hsp90 is overexpressed in cancer cells and may help to stabilize less stable proteins produced by DNA mutations. Molecular Formula: C 20 H 20 N 4 O 3. Ganetespib (also known as STA-9090) is a potent small-molecule inhibitor of heat shock protein 90 (IC50=4 nM). Description: Ganetespib, also known as STA-9090, is a synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. The HSP90 inhibitor ganetespib was provided by Synta Pharmaceuticals (Lexington, MA). On June 4, 2011, at the Annual Meeting of the American Society for Clinical Oncology (ASCO) a paper was presented on HSP-90 inhibitor ganetespib phase 2 non-small cell lung cancer trial results showing encouraging single agent clinical activity without eye or liver side effects. Phase 3. Combined P Unexpectedly, low-dose ganetespib also partially restores crizotinib sensitivity, both in vitro and in vivo, to cells and tumors expressing TKI-resistant MET mutants. Similar to the majority of small-molecule HSP90 inhibitors currently in development, ganetespib exhibits competitive binding with the N-domain ATP-binding pocket of HSP90, disrupting the chaperone cycle. Order now can get a discount! Cell Death Dis, 2021, 12(1):126 Cell Death Dis, 2021, 12(1):126 ... Christie, I., Kurland, B.F., Burns, T.F. To overcome this limitation, a clinically feasible method was sought to block HSP synthesis induced by the potent HSP90 inhibitor ganetespib. Ganetespib, under development by Synta, is a small molecule inhibitor of HSP90. Ganetespib is an investigational small molecule inhibitor of Hsp90 with favorable pharmacologic properties that distinguishes it from other first- and second-generation Hsp90 inhibitors in terms of potency, safety, and tolerability (27, 42). The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. Ganetespib is a novel, injectable, small molecule inhibitor of Hsp90 and is currently being investigated in adults with a broad range of tumor types with a … Two new-generation Hsp90 inhibitors, ganetespib and AT13387, are currently being evaluated as single or combinational therapies in … Ganetespib. Many oncogenic proteins rely on HSP90, and the inhibition of this molecule causes the degradation and death of these proteins. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. For research use only. In preclinical studies, ganetespib has demonstrated significant inhibition of cell proliferation and tumor growth in cell and xenograft models of multiple cancers ( 9 ). Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. the six selected HSP90 inhibitors and members of the HSP90 family (Supplementary Table 1). CAS Number: 888216-25-9. Ganetespib (formerly STA-9090) is a small-molecule inhibitor of Hsp90 with pharmacologic and biologic properties that distinguish it from other first- and second-generation inhibitors in terms of superior antitumor activity, potency, and safety (23). Ganetespib. Application: Ganetespib is a unique triazolone-containing Hsp90 inhibitor with an IC50 of 4 nM for OSA 8 cells. Ganetespib demonstrated potent in vitro cytotoxic activity (median rIC 50 8.8nM, range 4.4-27.1nM). The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. Hsp90 is a molecular chaperone required for the proper folding and activation of many cancer-promoting proteins, and is recognized as a key facilitator of cancer cell growth and survival. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. HSP90 inhibition with ganetespib has also resulted in decreased viability of KRAS-mutated cell lines by impacting downstream signaling through the mTOR and MEK pathways. Ganetespib is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-family Hsp90 inhibitors such as …
