1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECZC24832Cat. No.: HY-15294CAS No.: 1159824-67-5分式: CHFNOS分量: 364.4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 : 53 mg/mL (145.44 mM)* means soluble, but saturat

2、ion unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.7442 mL 13.7212 mL 27.4424 mL5 mM 0.5488 mL 2.7442 mL 5.4885 mL10 mM 0.2744 mL 1.3721 mL 2.7442 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 CZC24832種有效的選擇性 PI3K 抑制劑，IC50 為 27 nM，表觀解離常數(shù)(Kdapp) 為 19 nM。IC50 & Tar

3、get PI3K PI3K PI3K27 nM (IC50) 1.1 M (IC50) 8.194 M (IC50)體外研究CZC24832 is active in PI3K-dependent cellular C5a-induced AKT Ser473 phosphorylation (IC50=1.2 M)1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEand N-formyl-methionine-leucinephenylalanine (fMLP)-induced neutrophil migration assays (IC5

4、0=1.0 M)1.體內(nèi)研究 CZC24832 shows suitable pharmacokinetic properties including low clearance (0.84 L per h per kg bodyweight) and high oral bioavailability (37%), thus allowing further characterization of the inhibitor in rodentmodels of inflammation. In an IL-8-dependent air pouch model, CZC24832 show

5、s a dose-dependentreduction of granulocyte recruitment (80% inhibition at 10 mg per kg body weight) consistent with the degreeof inhibition observed in PI3K-null mice. Mice treated orally with 10 mg CZC24832 per kg body weight twiceper day show a substantial decrease of bone and cartilage destructio

6、n (53% reduction by histopathologicalanalysis) as well as of overall clinical parameters (38% reduction) 1.PROTOCOLCell Assay 1 RAW264.7 or THP-1 cells are starved for 2.5 h in serum-free medium before CZC24832 (0.1, 1, 10 and 100M) incubation for 30 min at 37C. RAW264.7 cells are then stimulated fo

7、r 3 min with C5a at a concentrationof 0.6 M, and THP-1 cells are stimulated with either insulin (1 uM, 10 min) or CSF (50 g/mL, 5 min) at 37Cand lysed on ice. The detection of AKT phosphorylation (Ser473) is performed using the iBlot system 1.MCE has not independently confirmed the accuracy of these

8、 methods. They are for reference only.Animal Rats 1Administration 1 Pharmacokinetics and oral bioavailability of CZC24832 are investigated in male Wistar rats followingadministration of a single intravenous (0.2 mg per kg body weight) or oral dose (10 mg per kg body weight).The dosing vehicle used i

9、s 0.5% (w/v) carboxymethyl cellulose in water for oral gavage. The intravenousdosing vehicle is 10% (v/v) DMSO in 30% (v/v) polyethylene glycol (PEG-400). Heparin blood forpharmacokinetic analysis is withdrawn retro-orbitally from mice or sublingually from rats to prepare plasmasamples. These are ho

10、mogenized with 10% (v/v) water and 3 volumes of acetonitrile and analyzed forCZC24832 by HPLC-MS/MS.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Bergamini G, et al. A selective inhibitor reveals PI3K dependence of T(H)17 cell differentiation. Nat Chem Biol. 2012 Apr 29;8(6):576-82.McePdfHeightCaution: Product has not been fully va