Ganetespib (STA-9090)

製品コードS1159 バッチS115904

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H20N4O3
分子量 364.4 CAS No. 888216-25-9
Solubility (25°C)* 体外 DMSO 73 mg/mL (200.32 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro The 50% inhibitory concentrations (IC50) for Ganetespib against malignant mast cell lines are 10-50 times lower than that for 17-AAG, indicating that triazolone class of HSP90 inhibitors likely exhibits greater potency than geldanamycin based inhibitors. [1] Ganetespib inhibits MG63 cell lines with IC50 of 43 nM. [1] Ganetespib binds to the ATP-binding domain at the N-terminus of Hsp90 and serves as a potent Hsp90 inhibitor by causing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2 and c-Met as well as Wilms' tumor 1. [2] Ganetespib, at low nanomolar concentrations, potently arrests cell proliferation and induces apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. Ganetespib exhibits potent cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. [3] Ganetespib treatment rapidly caused the degradation of known Hsp90 client proteins, exhibits superior potency to the ansamycin inhibitor 17-AAG, and shows sustained activity even with short exposure times.[3] In anohter study, Ganetespib induces apoptosis of malignant canine mast cell lines. Ganetespib is active at significantly lower concentrations for C2 and BR canine malignant mast cells with IC50 of 19 and 4 nM, respectively, while 17-AAG inhibits C2 and BR canine malignant mast cells with IC50 of 958 and 44 nM, respectively. [4] Both the expression of WT and mutant Kit are downregulated by 100 nM Ganetespib after 24 hours in all lines treated including C2 and BMCMCs cells. However, no effects on PI3K or HSP90 expression are observed following treatment with Ganetespib.[4]
in vivo Administration of Ganetespib leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore Ganetespib demonstrated better tumor penetration compared with tanespimycin.[2] Ganetespib inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. Ganetespib significantly inhibits tumor growth when dosed with two repeating cycles of 25 mg/kg/day for 3 days, with a %T/C value of 18. Ganetespib is well-tolerated, with the vehicle and Ganetespib groups having average bodyweight changes relative to the start of the study of +0.3% and -8.1% on day 17, respectively.[4]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 OSA cells
濃度 0.001-1μM
反応時間 5 days
実験の流れ A total of 1.5 × 103 OSA cells are seeded in 96-well plates in 10% serum-containing complete medium and incubated overnight to determine the 50% inhibitory concentrations. Plates are, harvested at day 5 following 0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 μM Ganetespib, treatment and analyzed. Fluorescence measurements are made using a plate reader with excitation at 485 nm and emission detection at 530 nm. Relative cell number is calculated as a percentage of the control wells: absorbance of sample/absorbance of DMSO treated cells × 100.
動物実験 動物モデル Female severe combined immune-deficient (SCID) mice
投薬量 25 mg/kg/day for 3 days
投与方法 Tail vein injection

カスタマーフィードバック

Data from [Data independently produced by Cancer Res, 2014, 10.1158/0008-5472.CAN-14-1017]

Data from [Data independently produced by , , Cell, 2017, 168(5):856-866]

Data from [Data independently produced by , , Hum Mol Genet, 2015, 10.1093/hmg/ddv136]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

HSP90 inhibition suppresses tumor glycolytic flux to potentiate the therapeutic efficacy of radiotherapy for head and neck cancer [ Sci Adv, 2024, 10(8):eadk3663] PubMed: 38394204
The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma [ Nat Commun, 2023, 14(1):1516] PubMed: 36934113
The Hsp90 molecular chaperone governs client proteins by targeting intrinsically disordered regions [ Mol Cell, 2023, S1097-2765(23)00377-5] PubMed: 37295430
Mutant p53-ENTPD5 control of the calnexin/calreticulin cycle: a druggable target for inhibiting integrin-α5-driven metastasis [ J Exp Clin Cancer Res, 2023, 42(1):203] PubMed: 37563605
Shear stress induces monocyte/macrophage-mediated inflammation by upregulating cell-surface expression of heat shock proteins [ Biomed Pharmacother, 2023, 161:114566] PubMed: 36963359
Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: Implications from preclinical data for a novel therapeutic approach [ Biomed Pharmacother, 2023, 164:114918] PubMed: 37216705
Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration [ Cells, 2023, 12(2)212] PubMed: 36672148
Cytokine-Induced Killer Cells in Combination with Heat Shock Protein 90 Inhibitors Functioning via the Fas/FasL Axis Provides Rationale for a Potential Clinical Benefit in Burkitt's lymphoma [ Int J Mol Sci, 2023, 24(15)12476] PubMed: 37569852
Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy [ Int J Mol Sci, 2023, 24(18)13830] PubMed: 37762133
HSP90 C-terminal domain inhibition promotes VDAC1 oligomerization via decreasing K274 mono-ubiquitination in Hepatocellular Carcinoma [ Neoplasia, 2023, 44:100935] PubMed: 37717471

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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