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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (13.72mM) Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 (STA-9090) 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] It inhibits MG63 cell lines with IC50 of 43 nM. [1] This compound 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] At low nanomolar concentrations, it 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. It 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] Treatment with this compound 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, it induces apoptosis of malignant canine mast cell lines. It 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 it.[4]
in vivo Ganetespib (STA-9090) administration leads to significant tumor shrinkage in several tumor xenograft models in mice and appears to be less toxic. Furthermore, it demonstrated better tumor penetration compared with tanespimycin.[2] This compound inhibits in vivo tumor growth in both malignant mast cell and OSA xenograft models. It 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 treatment 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 To determine the 50% inhibitory concentrations, a total of 1.5 × 103 OSA cells are seeded in 96-well plates in 10% serum-containing complete medium and incubated overnight. Plates are harvested at day 5 following treatment with 0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 μM Ganetespib (STA-9090) 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/19544563/
  • https://pubmed.ncbi.nlm.nih.gov/21154128/
  • https://pubmed.ncbi.nlm.nih.gov/22144665/
  • https://pubmed.ncbi.nlm.nih.gov/18657349/

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：

Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress [ Nat Neurosci, 2025, 28(6):1174-1184] PubMed: 40456907
Hsp90 C-terminal domain inhibition enhances ferroptosis by disrupting GPX4-VDAC1 interaction to increase HMOX1 release from oligomerized VDAC1 channels [ Redox Biol, 2025, 85:103672] PubMed: 40472773
In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [11C]HSP990 in Healthy Aging and Neurodegeneration [ J Nucl Med, 2025, jnumed.124.268961] PubMed: 40306968
HSC70 coordinates COP9 signalosome and SCF ubiquitin ligase activity to enable a prompt stress response [ EMBO Rep, 2025, 10.1038/s44319-025-00376-x] PubMed: 39915298
Heat shock protein 90 chaperone activity is required for hepatitis A virus replication [ J Virol, 2025, e0050225] PubMed: 40470959
Curcumin Induces Homologous Recombination Deficiency by BRCA2 Degradation in Breast Cancer and Normal Cells [ Cancers (Basel), 2025, 17(13)2109] PubMed: 40647408
Targeting HSP90 with Ganetespib to Induce CDK1 Degradation and Promote Cell Death in Hepatoblastoma [ Cancers (Basel), 2025, 17(8)1341] PubMed: 40282517
Targeting heat shock protein 90 with usnic acid relieves immune suppression via aryl hydrocarbon receptor-mediated mechanisms in lung cancer [ Mol Biomed, 2025, 6(1):81] PubMed: 41091398
ETS1 Orchestrates a Hybrid EMT Program Driving in vivo Metastasis and Immune Evasion [ bioRxiv, 2025, 2025.07.17.665404] PubMed: 40777467
Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption [ Elife, 2024, 12RP86194] PubMed: 39713930

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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