Pimitespib (TAS-116)

製品コードS7716 バッチS771601

印刷

化学情報

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

C25H26N8O
分子量 454.53 CAS No. 1260533-36-5
Solubility (25°C)* 体外 DMSO 91 mg/mL (200.2 mM)
Ethanol 11 mg/mL (24.2 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml 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. 
Clear solution
5% DMSO 95% Corn oil
0.6mg/ml Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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 Pimitespib (TAS-116) is a novel, small-molecule HSP90 inhibitor which inhibits geldanamycin-FITC binding to HSP90 proteins with Ki values of 34.7 nmol/L, 21.3 nmol/L, >50,000 nmol/L, and >50,000 nmol/L for HSP90α, HSP90β, GRP94, and TRAP1, respectively. Furthermore, TAS-116 does not inhibit other ATPases such as HSP70 (IC50 >200 μmol/L).
in vitro

TAS-116 is a selective inhibitor of cytosolic HSP90α and β that does not inhibit HSP90 paralogs such as endoplasmic reticulum GRP94 or mitochondrial TRAP1. Treatment of HCT116 cells with 0.3 μmol/L TAS-116 for 8 hours results in reduced levels of DDR1, which interacts with HSP90α and induction of HSP70, which is a surrogate marker of cytosolic HSP90 inhibition[1].
in vivo

Oral administration of TAS-116 leads to tumor shrinkage in human tumor xenograft mouse models accompanied by depletion of multiple HSP90 clients. In a rat model, the antitumor activity of TAS-116 is accompanied by a higher distribution of the compound in subcutaneously xenografted NCI-H1975 non-small cell lung carcinoma tumors than in retina. TAS-116 shows activity against orthotopically transplanted NCI-H1975 lung tumors. Pharmacokinetic profiling of TAS-116 in rodent and nonrodent species shows that TAS-116 is orally absorbed and had a bioavailability of almost 100% in mice, 69.0% in rats, and 73.9% in dogs without special formulation. In a HER2-expressing NCI-N87 human gastric cancer xenograft mouse model, chronic administration of TAS-116 is tolerable, with the average weight loss in mice not exceeding 10% during the treatment period[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HCT116 cells
濃度 0.3, 1 and 3 μM
反応時間 8 hours
実験の流れ

HCT116 cells are treated with TAS-116 or 17-AAG for 8 hours. Western blotting is performed by using 10 μg of cell lysate.
動物実験 動物モデル Six-week-old male BALB/c nude mice subcutaneously implanted with cancer cells
投薬量 3.6 to 14.0 mg/kg/day
投与方法 oral

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：

Syringaresinol inhibits cardiorenal fibrosis through HSP90 in a cardiorenal syndrome type 2 [ Hum Exp Toxicol, 2023, 42:9603271231165678] PubMed: 36960691
Single-cell dissection of the multiomic landscape of high-grade serous ovarian cancer [ Cancer Res, 2022, CAN-21-3819] PubMed: 35969151

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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