WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202703
Description: Ganetespib, also known as 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.
MedKoo Cat#: 202703
Name: Ganetespib (STA-9090)
Chemical Formula: C20H20N4O3
Exact Mass: 364.15354
Molecular Weight: 364.4
Elemental Analysis: C, 65.92; H, 5.53; N, 15.38; O, 13.17
Synonym: STA9090; STA 9090; STA-9090; Ganetespib
IUPAC/Chemical Name: 5-[2,4-dihydroxy-5-(1-methylethyl)phenyl]-4-(1-methyl-1H-indol-5-yl)-2,4-dihydro-3H- 1,2,4-triazol-3-one
InChi Key: RVAQIUULWULRNW-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C1NN=C(C2=CC(C(C)C)=C(O)C=C2O)N1C3=CC4=C(N(C)C=C4)C=C3
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||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 vitro activity:||JAK kinases are established Hsp90 client proteins and here we show that the novel small molecule Hsp90 inhibitor ganetespib (formerly STA-9090) exhibits potent in vitro 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 JAK2(V617F) mutant, with subsequent loss of STAT activity and reduced STAT-target gene expression. The NCI-H1975 non-small cell lung cancer (NSCLC) cell line expresses the Hsp90 client EGFRL858R/T790M, a constitutively activated and erlotinib-resistant form of EGFR, and ganetespib treatment resulted in a dose-dependent decrease in EGFR expression in these cells (Fig. 2A). Moreover, ganetespib also induced potent degradation of JAK2 and loss of phosphorylated STAT3 in a dose-dependent manner. Inactivation of AKT and GSK3β, proteins important in regulating apoptosis, was observed with a similar dose response to that of JAK2/STAT3 signaling. Recently it was shown that JAK2 can modulate the activity of additional apoptotic regulators such as BAD and BCL-XL to promote cell survival. Consistent with this, a concomitant reduction was detected in the levels of phosphorylated BAD (Fig. 2A), thus reducing the pro-apoptotic activity of this protein. These data suggest a potential mechanism to account for the cytotoxic response observed with ganetespib treatment (Fig. 1A). Response: PLoS One. 2011 Apr 14;6(4):e18552. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21533169/|
|In vivo activity:||In mice bearing NCI-H1975 (EGFR L858R/T790M) xenografts, ganetespib was rapidly eliminated from plasma and normal tissues but was maintained in tumor with t(1/2) 58.3 hours, supporting once-weekly dosing experiments, in which ganetespib produced greater tumor growth inhibition than 17-AAG. However, after a single dose, reexpression of mutant EGFR occurred by 72 hours, correlating with reversal of antiproliferative and proapoptotic effects. Consecutive day dosing resulted in xenograft regressions, accompanied by more sustained pharmacodynamic effects. Ganetespib also showed activity against mouse lung adenocarcinomas driven by oncogenic ERBB2 YVMA. Reference: Clin Cancer Res. 2012 Sep 15;18(18):4973-85. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22806877/|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 364.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Proia DA, Foley KP, Korbut T, Sang J, Smith D, Bates RC, Liu Y, Rosenberg AF, Zhou D, Koya K, Barsoum J, Blackman RK. Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling. PLoS One. 2011 Apr 14;6(4):e18552. doi: 10.1371/journal.pone.0018552. PMID: 21533169; PMCID: PMC3077378. 2. Shimamura T, Perera SA, Foley KP, Sang J, Rodig SJ, Inoue T, Chen L, Li D, Carretero J, Li YC, Sinha P, Carey CD, Borgman CL, Jimenez JP, Meyerson M, Ying W, Barsoum J, Wong KK, Shapiro GI. Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer. Clin Cancer Res. 2012 Sep 15;18(18):4973-85. doi: 10.1158/1078-0432.CCR-11-2967. Epub 2012 Jul 17. PMID: 22806877; PMCID: PMC3477583.|
|In vivo protocol:||1. Shimamura T, Perera SA, Foley KP, Sang J, Rodig SJ, Inoue T, Chen L, Li D, Carretero J, Li YC, Sinha P, Carey CD, Borgman CL, Jimenez JP, Meyerson M, Ying W, Barsoum J, Wong KK, Shapiro GI. Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer. Clin Cancer Res. 2012 Sep 15;18(18):4973-85. doi: 10.1158/1078-0432.CCR-11-2967. Epub 2012 Jul 17. PMID: 22806877; PMCID: PMC3477583. 2. Ying W, Du Z, Sun L, Foley KP, Proia DA, Blackman RK, Zhou D, Inoue T, Tatsuta N, Sang J, Ye S, Acquaviva J, Ogawa LS, Wada Y, Barsoum J, Koya K. Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther. 2012 Feb;11(2):475-84. doi: 10.1158/1535-7163.MCT-11-0755. Epub 2011 Dec 5. PMID: 22144665.|
1: Xiang L, Gilkes DM, Chaturvedi P, Luo W, Hu H, Takano N, Liang H, Semenza GL. Ganetespib blocks HIF-1 activity and inhibits tumor growth, vascularization, stem cell maintenance, invasion, and metastasis in orthotopic mouse models of triple-negative breast cancer. J Mol Med (Berl). 2013 Nov 20. [Epub ahead of print] PubMed PMID: 24248265.
2: Proia DA, Zhang C, Sequeira M, Jimenez JP, He S, Spector NL, Shapiro GI, Tolaney S, Nagai M, Acquaviva J, Smith DL, Sang J, Bates RC, El-Hariry I. Preclinical activity profile and therapeutic efficacy of the Hsp90 inhibitor ganetespib in triple-negative breast cancer. Clin Cancer Res. 2013 Oct 30. [Epub ahead of print] PubMed PMID: 24173541.
3: Lai CH, Park KS, Lee DH, Alberobello AT, Raffeld M, Pierobon M, Pin E, Petricoin Iii EF, Wang Y, Giaccone G. HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer. Oncogene. 2013 Oct 28. doi: 10.1038/onc.2013.439. [Epub ahead of print] PubMed PMID: 24166505.
4: Miyajima N, Tsutsumi S, Sourbier C, Beebe K, Mollapour M, Rivas C, Yoshida S, Trepel JB, Huang Y, Tatokoro M, Shinohara N, Nonomura K, Neckers L. The HSP90 Inhibitor Ganetespib Synergizes with the MET Kinase Inhibitor Crizotinib in both Crizotinib-Sensitive and -Resistant MET-Driven Tumor Models. Cancer Res. 2013 Dec 1;73(23):7022-33. doi: 10.1158/0008-5472.CAN-13-1156. Epub 2013 Oct 11. PubMed PMID: 24121490.
5: Ganetespib AIDS lung cancer survival. Cancer Discov. 2013 Jul;3(7):OF7. doi: 10.1158/2159-8290.CD-NB2013-085. Epub 2013 Jun 6. PubMed PMID: 23847382.
6: Nagaraju GP, Park W, Wen J, Mahaseth H, Landry J, Farris AB, Willingham F, Sullivan PS, Proia DA, El-Hariry I, Taliaferro-Smith L, Diaz R, El-Rayes BF. Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1α and STAT-3. Angiogenesis. 2013 Oct;16(4):903-17. doi: 10.1007/s10456-013-9364-7. Epub 2013 Jul 10. Erratum in: Angiogenesis. 2013 Oct;16(4):919. Ganji, Purnachandra Nagaraju [corrected to Nagaraju, Ganji Purnachandra]. PubMed PMID: 23838996.
7: Friedland JC, Smith DL, Sang J, Acquaviva J, He S, Zhang C, Proia DA. Targeted inhibition of Hsp90 by ganetespib is effective across a broad spectrum of breast cancer subtypes. Invest New Drugs. 2013 May 18. [Epub ahead of print] PubMed PMID: 23686707.
8: Socinski MA, Goldman J, El-Hariry I, Koczywas M, Vukovic V, Horn L, Paschold E, Salgia R, West H, Sequist LV, Bonomi P, Brahmer J, Chen LC, Sandler A, Belani CP, Webb T, Harper H, Huberman M, Ramalingam S, Wong KK, Teofilovici F, Guo W, Shapiro GI. A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin Cancer Res. 2013 Jun 1;19(11):3068-77. doi: 10.1158/1078-0432.CCR-12-3381. Epub 2013 Apr 3. PubMed PMID: 23553849.
9: Goldman JW, Raju RN, Gordon GA, El-Hariry I, Teofilivici F, Vukovic VM, Bradley R, Karol MD, Chen Y, Guo W, Inoue T, Rosen LS. 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. BMC Cancer. 2013 Mar 25;13:152. doi: 10.1186/1471-2407-13-152. PubMed PMID: 23530663; PubMed Central PMCID: PMC3626541.
10: Wu X, Marmarelis ME, Hodi FS. Activity of the heat shock protein 90 inhibitor ganetespib in melanoma. PLoS One. 2013;8(2):e56134. doi: 10.1371/journal.pone.0056134. Epub 2013 Feb 13. PubMed PMID: 23418523; PubMed Central PMCID: PMC3572008.