TG100-115 - PI3K 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETG100-115Cat. No.: HY-10111CAS No.: 677297-51-7分式: CHNO分量: 346.34作靶點(diǎn): PI3K作通路: PI3K/Akt/mTOR儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 5.45 mg/mL (15.74 mM; Need ultrasonic and warming

2、)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.8873 mL 14.4367 mL 28.8734 mL5 mM 0.5775 mL 2.8873 mL 5.7747 mL10 mM 0.2887 mL 1.4437 mL 2.8873 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 TG100-115種選擇性的 PI3K/PI3K 抑制劑，IC50 分別為 83 和 235 nM。IC50 & Target PI3K PI3K83 nM (I

3、C50) 235 nM (IC50)體外研究TG100-115 inhibits PI3K and PI3K with IC50s of 83 and 235 nM, respectively, whereas both PI3K andPI3K are relatively unaffected (IC50 values 1 M). As a gauge of general specificity, TG100-115 is also1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEassayed against a 133 protein

4、kinase panel, none of which are inhibited at IC50 values 1.體內(nèi)研究 To correlate these in vivo responses with the molecular target of interest, PI3K pathway signaling ismonitored through western blot analyses of Akt phosphorylation (a PI3K-mediated event). VEGF injection i.v.in mice induces a rapid Akt

5、phosphorylation readily detectable in lung lysates, pretreatment with TG100-115blocks this response. Blockade is seen with TG100-115 doses as low as 0.5 mg/kg and persists over aperiod of several hours. In initial dose-ranging studies, generally equivalent responses are observed usingTG100-115 doses

6、 of 0.5-10 mg/kg, and we therefore elected to conduct a statistically powered test at thelowest dose. Animals dosed with TG100-115 as a single 0.5 mg/kg i.v. bolus 30 min after reperfusiondeveloped smaller infarcts vs. vehicle-treated controls. Measuring infarct area as percent of total LV ischemica

7、rea, infarct size is reduced by 35% (P=0.04). Viable tissue within the ischemic zone is increased by 37%(P=0.04), directly demonstrating the cardioprotective effect of PI3K/ inhibition 1.PROTOCOLKinase Assay 1 PI3K reactions are constructed by using recombinant human kinases, 3 M ATP, phosphatidylin

8、ositolsubstrate, and cofactors, and reaction progression measured by using a luminescent-based detection systemto quantify ATP consumption. Protein kinase assays are performed by using commercial screening services1.MCE has not independently confirmed the accuracy of these methods. They are for refe

9、rence only.Cell Assay 1 Human umbilical vein EC plated in 96-well cluster plates (5,000 cells/well) are cultured in assay medium(containing 0.5% serum and 50 ng/mL VEGF) in the presence or absence of test compounds (e.g., TG100-115) (10 M), and cell numbers are quantified by XTT assay 24, 48, or 72

10、h later 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 Sprague-Dawley rats (175-200 g) are dosed i.v. with either TG100-115 (1 mg/kg) or vehicle, and 1-4 h laterEvans blue dye is administered i.v. as 500 l of a 2% steril

11、e saline solution. Immediately after dye injection,animals are injected intradermally on each shaved flank with 100 L of saline, VEGF (2 g/mL stock), orhistamine (10 g/mL stock). Thirty minutes later, injection sites are photographed.MCE has not independently confirmed the accuracy of these methods.

12、 They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Doukas J, et al. Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury. ProcNatl Acad Sci U S A. 2006 Dec 26;103(52):19866-71.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMcePdfHeightCauti