"目录号: HY-15205
Cell Cycle/DNA DamageMetabolic Enzyme/Protease-
Ganetespib 是一种独特的热休克蛋白 90(HSP90) 抑制剂，在 OSA 8 细胞中，其IC50值为 4 nM。
HSP
相关产品
17-AAG-Triptolide-NVP-AUY922-Geldanamycin-Teprenone-Rocaglamide-VER-155008-AT13387-Retaspimycin Hydrochloride-Alvespimycin hydrochloride-Debio 0932-BIIB021-PU-H71-NVP-HSP990-Apoptozole-
生物活性
Description
Ganetespib is a unique non-geldanamycin heat shock protein 90 (HSP90) inhibitor, withIC50of 4 nM in OSA 8 cells.
In Vitro
Ganetespib causes depletion of receptor tyrosine kinases, extinguishing of downstream signaling, inhibition of proliferation and induction of apoptosis with IC50values ranging 2-30 nM in genomically-defined NSCLC cell lines. Ganetespib is also approximately 20-fold more potent in isogenic Ba/F3 pro-B cells rendered IL-3 independent by expression of EGFR and ERBB2 mutants[1]. Ganetespib exhibits potent in vitro cytotoxicity in a range of solid and hematologic tumor cell lines, induces the degradation of known Hsp90 client proteins, displays superior potency to the ansamycin inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)[2]. Ganetespib is a potent HSP90 inhibitor, and shown to kill canine tumor cell lines in vitro[3]. Ganetespib possesses superior JAK/STAT inhibitory activity to both P6 and 17-AAG in terms of potency or duration of response in the HEL92.1.7 cells[4].
In Vivo
Ganetespib (125 mg/kg, i.v.) accumulates in tumors relative to normal tissues and displays greater in vivo efficacy than 17-AAG without increased toxicity and inhibits proliferation and induces apoptosis in parallel with EGFR depletion in NCI-H1975 xenografts[1]. Ganetespib (100, 125, 150 mg/kg, i.v.) shows potent antitumor efficacy in solid and hematologic xenograft models of oncogene addiction, as evidenced by significant growth inhibition and/or regressions[2].
Clinical Trial
NCT01554969
Emory University-Synta Pharmaceuticals Corp.
Rectal Cancer
May 2012
Phase 1
NCT01485835
Emory University-Multiple Myeloma Research Consortium-Synta Pharmaceuticals Corp.
Multiple Myeloma
January 2012
Phase 1
NCT02008877
Sarcoma Alliance for Research through Collaboration-Synta Pharmaceuticals Corp.-United States Department of Defense
Malignant Peripheral Nerve Sheath Tumors (MPNST)-Sarcoma
December 2013
Phase 1-Phase 2
NCT01560416
Dana-Farber Cancer Institute
Breast Cancer
May 2012
Phase 2
NCT01562015
Synta Pharmaceuticals Corp.
Non Small Cell Lung Cancer
April 2012
Phase 2
NCT02261805
Georgetown University-Synta Pharmaceuticals Corp.
Cancer-Small Cell Lung Cancer
October 2014
Phase 1-Phase 2
NCT01798485
Synta Pharmaceuticals Corp.
Non-Small-Cell Lung Adenocarcinoma-Non-small Cell Lung Cancer Stage IIIB-Non-small Cell Lung Cancer Stage IV-Non-small Cell Lung Cancer Metastatic
April 2013
Phase 3
NCT01039519
Synta Pharmaceuticals Corp.
Gastrointestinal Stromal Tumor
January 2010
Phase 2
NCT01579994
Memorial Sloan Kettering Cancer Center
Advanced Lung Cancer
April 2012
Phase 1
NCT02334319
Emory University-Synta Pharmaceuticals Corp.
Stage I Hypopharyngeal Squamous Cell Carcinoma-Stage I Laryngeal Squamous Cell Carcinoma-Stage I Oral Cavity Squamous Cell Carcinoma-Stage I Oropharyngeal Squamous Cell Carcinoma-Stage II Hypopharyngeal Squamous Cell Carcinoma-Stage II Laryngeal Squamous Cell Carcinoma-Stage II Oral Cavity Squamous Cell Carcinoma-Stage II Oropharyngeal Squamous Cell Carcinoma-Stage III Hypopharyngeal Squamous Cell Carcinoma-Stage III Laryngeal Squamous Cell Carcinoma-Stage III Oral Cavity Squamous Cell Carcinoma
December 2014
Phase 1
NCT01962948
Fox Chase Cancer Center-National Cancer Institute (NCI)
Recurrent Fallopian Tube Cancer-Recurrent Ovarian Epithelial Cancer-Recurrent Primary Peritoneal Cavity Cancer
October 9, 2013
Phase 1-Phase 2
NCT02389751
M.D. Anderson Cancer Center-Synta Pharmaceuticals Corp.
Esophageal Cancer
April 2015
Phase 1
NCT02060253
Memorial Sloan Kettering Cancer Center-National Cancer Institute (NCI)-Synta Pharmaceuticals Corp.-New York University Cancer Institute
HER2-positive Breast Cancer-Male Breast Cancer-Recurrent Breast Cancer-Stage IIIA Breast Cancer-Stage IIIB Breast Cancer-Stage IIIC Breast Cancer-Stage IV Breast Cancer
April 2014
Phase 1
NCT01183364
Synta Pharmaceuticals Corp.
Solid Tumor Malignancies
July 2010
Phase 1
NCT00688116
Synta Pharmaceuticals Corp.
Solid Tumors
October 2007
Phase 1
NCT01677455
Synta Pharmaceuticals Corp.
Breast Cancer-HER-2 Positive Breast Cancer-Triple Negative Breast Cancer-ER/Progressive Response (PR) + Refractory to Prior Hormonal Treatment
July 2012
Phase 2
NCT01590160
University College, London-Cancer Research UK
Lung Cancer - Malignant Pleural Mesothelioma
August 2013
Phase 1-Phase 2
NCT02012192
Medical University Innsbruck-European Commission
Epithelial Ovarian Cancer-Fallopian Tube Cancer-Primary Peritoneal Cancer
June 2014
Phase 1-Phase 2
NCT01348126
Synta Pharmaceuticals Corp.
Non-small Cell Lung Cancer Stage IIIB-Non-small Cell Lung Cancer Stage IV-Non-small Cell Lung Cancer Metastatic
May 2011
Phase 2-Phase 3
NCT00858572
Synta Pharmaceuticals Corp.
AML-CML-MDS-Myeloproliferative Disorders
March 2009
Phase 1
NCT02192541
National Cancer Institute (NCI)-National Institutes of Health Clinical Center (CC)
Neoplasms
July 9, 2014
Phase 1
NCT01236144
Cardiff University-Leukaemia & Lymphoma Research Group-Experimental Cancer Medicine Centre Network
Acute Myeloid Leukaemia-High Risk Myelodysplastic Syndrome
April 2011
Phase 1-Phase 2
NCT00964873
Synta Pharmaceuticals Corp.
Acute Myeloid Leukemia-Acute Lymphoblastic Leukemia-Blast-phase Chronic Myelogenous Leukemia-AML-ALL-CML
August 2009
Phase 1
NCT02637375
University of Chicago
Breast Cancer
May 2016
NCT02272478
Cardiff University-Cancer Research UK
Acute Myeloid Leukaemia-Myelodysplastic Syndrome
October 2014
Phase 3
NCT01042379
QuantumLeap Healthcare Collaborative
Breast Neoplasms-Breast Cancer-Breast Tumors
March 2010
Phase 2
NCT01031225
Synta Pharmaceuticals Corp.
Non Small Cell Lung Cancer
November 2009
Phase 2
NCT01167114
Massachusetts General Hospital-Dana-Farber Cancer Institute-Beth Israel Deaconess Medical Center-Synta Pharmaceuticals Corp.
Esophagogastric Cancer
August 2010
Phase 2
NCT01665937
Massachusetts General Hospital-Dana-Farber Cancer Institute-Beth Israel Deaconess Medical Center-Synta Pharmaceuticals Corp.
Hepatocellular Carcinoma
August 2010
Phase 1
NCT01273896
Memorial Sloan Kettering Cancer Center-Synta Pharmaceuticals Corp.
Breast Cancer
January 2011
Phase 2
NCT01111838
Memorial Sloan Kettering Cancer Center-Synta Pharmaceuticals Corp.
Colon Cancer-Rectal Cancer
April 2010
Phase 2
NCT00687934
Synta Pharmaceuticals Corp.
Solid Tumors
October 2007
Phase 1
NCT01173523
David M. Jackman, MD-Massachusetts General Hospital-Beth Israel Deaconess Medical Center-Synta Pharmaceuticals Corp.-Dana-Farber Cancer Institute
Small Cell Lung Cancer
July 28, 2010
Phase 2
NCT01551693
Dana-Farber Cancer Institute-Synta Pharmaceuticals Corp.
Melanoma
September 2011
Phase 2
NCT01200238
Dana-Farber Cancer Institute-Beth Israel Deaconess Medical Center-Massachusetts General Hospital-Brigham and Women's Hospital-Synta Pharmaceuticals Corp.
Ocular Melanoma
June 2010
Phase 2
NCT01270880
Barbara Ann Karmanos Cancer Institute-National Cancer Institute (NCI)
Adenocarcinoma of the Prostate-Hormone-resistant Prostate Cancer-Recurrent Prostate Cancer-Stage IV Prostate Cancer
January 2011
Phase 2
NCT01227018
Vanderbilt-Ingram Cancer Center-National Cancer Institute (NCI)
Adenocarcinoma of the Pancreas-Recurrent Pancreatic Cancer-Stage IV Pancreatic Cancer
December 2010
Phase 2
NCT01368003
Toni Choueiri, MD-Dana-Farber Cancer Institute
Adenocarcinoma of the Prostate
April 2011
Phase 2
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References
[1].Shimamura T, et al. Ganetespib (STA-9090), a Non-Geldanamycin HSP90 Inhibitor, has Potent Antitumor Activity in In Vitro and In Vivo Models of Non-Small Cell Lung Cancer. Clin Cancer Res. 2012 Jul 17.
[2].Ying W, et al. 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.
[3].London CA, et al. Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer.PLoS One. 2011;6(11):e27018.
[4].Proia DA, et al. 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.