AS-252424 - PI3K 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAS-252424Cat. No.: HY-13532CAS No.: 900515-16-4分式: CHFNOS分量: 305.28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 : 57 mg/mL (186.71 mM)* means soluble, but satura

2、tion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 3.2757 mL 16.3784 mL 32.7568 mL5 mM 0.6551 mL 3.2757 mL 6.5514 mL10 mM 0.3276 mL 1.6378 mL 3.2757 mL請根據(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，并請注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AS-252424種有效的選擇性 PI3K 抑制劑，IC50 為 3010 nM。IC50 & Target PI3K PI3K PI3K

3、 PI3K935 nM (IC50) 30 nM (IC50) 20 M (IC50) 20 M (IC50)體外研究AS-252424 also inhibits PI3K, PI3K and PI3K with IC50s of 935150 nM, 20 M and 20 M, respectively.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEAS-252424 inhibits MCP-1-mediated chemotaxis in wild-type primary monocytes in a concentration-

4、dependent manner with an IC50 value of 52 M, as well as in the monocytic cell line THP-1 with an IC50value of 53 M. In the human monocytic cell line THP-1, MCP-1 binding to the GPCR chemokine receptorCCR2, strongly induces phosphorylation of PKB/Akt, which is effectively inhibited by AS-252424 at IC

5、50values as low as 0.4 M. In contrast, induction of PKB/Akt phosphorylation by colony stimulating factor (CSF-1), binding to the growth factor receptor c-fms, is only blocked by AS-252424 at IC50 values as high as 4.7 M 1.體內(nèi)研究 Oral administration of AS-252424 in a mouse model of acute peritonitis le

6、ads to a significant reduction ofleukocyte recruitment. To evaluate the efficacy of AS-252424 to block leukocyte migration in vivo, it is testedin a mouse model of thioglycollate-induced peritonitis. Oral administration of AS-252424 at 10 mg/kg resultsin moderate reduction of neutrophil recruitment

7、(35%14%), almost matching the result observed in PI3K-deficient mice. Given the short oral half-life of AS-252424 (t1/2=1 h) and relative high clearance (2.25 L/kgper h), investigations at later time points (24-48 h) to assess macrophage and monoycyte recruitment are notundertaken. The modest pharma

8、cokinetic properties do not appear to be caused by rapid oxidativemetabolism (microsomal metabolism after 1 h: 16% (rat), 10% (human) 1.PROTOCOLKinase Assay 1 A PI3K lipid kinase assay, based on the neomycin-coated scintillation proximity assay (SPA) beadtechnology, is performed in 384-well plates u

9、sing ATP/33PATP and PtdIns. Kinase assays for IC50 valuedeterminations with PI3K, PI3K, and PI3K are carried out 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 After 3 h of starvation in serum-free medium, Raw-264 macrophages are pretrea

10、ted with inhibitors (e.g., AS-252424, 1 nM, 10 nM, 100 nM, 1 M, 10 M and 100 M) or DMSO for 30 min and stimulated for 5 min with50 nM C5a. PKB/Akt phosphorylation is monitored using phospho-Ser-473 Akt specific antibody andstandard ELISA protocols 1.MCE has not independently confirmed the accuracy o

11、f these methods. They are for reference only.Animal Mice 1Administration 1 PI3K knockout (KO) mice are used. Oral administration of AS-252424 at 10 mg/kg is performed in PI3K-deficient mice.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J M

12、ol Med (Berl). 2018 Feb;96(2):119-133.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Pomel V, et al. Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma. JMed Chem. 2006 Jun 29;49(13):3857-71.McePdfHeightCaution: