1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECPI-203Cat. No.: HY-15846CAS No.: 1446144-04-2分式: CHClNOS分量: 399.9作靶點(diǎn): Epigenetic Reader Domain作通路: Epigenetics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 : 47 mg/mL (117.53 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.5006 mL 12.5031 mL 25.0063 mL5 mM 0.5001 mL 2.5006 mL 5.0013 mL10 mM 0.2501 mL 1.2503 mL 2.5006 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 CPI-203種有效的，選擇性的，細(xì)胞通透的 BET bromodomain 抑制劑，抑制 BRD4，I

3、C50 值約為 37nM。IC50 & Target IC50: 37 nM (BRD4)體外研究CPI203 inhibits BRD4 in vitro and in cells, but does not affect BRD4 kinase activity in vitro 1. CPI203 exerts1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEa cytostatic effect in all the 9 MCL cell lines analyzed with GI50 ranging from 0.06 to 0.71

4、 M, with lowcytotoxicity in normal PBMCs from healthy donors. Furthermore, lenalidomide and CPI203, by targeting IRF4and MYC, efficiently activates the cell death program in MCL cells resistant to bortezomib 2.體內(nèi)研究 BRD4 mediates CTD Ser2 phosphorylation in vivo 1. In REC-1 tumor-bearing mice, the co

5、mbination oflenalidomide with CPI203 (2.5 mg/kg, i.p.) synergistically augments the antitumoral properties of each singleagent via the abrogation of MYC and IRF4 expression and the induction of apoptosis 2.PROTOCOLKinase Assay 1 In vitro kinase assays with BRD4, PTEFb, and TFIIH are performed in 20

6、L 50 mM Tris, pH 7.5, 5 mM DTT,5 mM MnCl2, and 5 mM MgCl2 with 10 Ci 32P ATP (6,000 Ci/mM) and/or 40 M ATP where indicated.The kinase reactions are incubated for 1 h at 30C, and then, the proteins are resolved by SDS/PAGE; theextent of phosphorylation is quantitated by a phosphorimager. For kinetic

7、measurements, the quantitatedvalues are plotted on a Lineweaver-Burke plot to calculate Vmax and Km values. When kinase inhibitors areused, appropriate dilutions of the inhibitor are added at the start of the kinase reaction. Mock-treated kinasereactions are treated with equivalent volumes of DMSO.M

8、CE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 MCL primary cells (1.5105) and cell lines (4104) are incubated as indicated with lenalidomide and/orPI203. MTT (3-(4,5-dimethylthiazolyl- 2)-2,5-diphenyltetrazolium bromide) reagent is added fo

9、r 2-6 additionalhours before spectrophotometric measurement. Each measurement is made in triplicate. Values arerepresented using untreated control cells as reference. The GI50 is calculated as the concentration thatproduced 50% growth inhibition. Combination indexes (CIs) are calculated by using the

10、 Calcusyn softwareversion 2.0.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal CB17-severe combined immunodeficiency (SCID) mice are inoculated subcutaneously with 107 cells of theAdministration 2 indicated MCL cell line, and monitored for tumor g

11、rowth and vital parameters as previously described. Forlenalidomide and lenalidomide-bortezomib dosing, mice are randomly assigned into cohorts of 3-4 mice eachand receive by intraperitoneal injection a twice weekly dose of bortezomib (0.15 mg/kg), a daily dose oflenalidomide (50 mg/kg), the combina

12、tion of lenalidomide and bortezomib, or an equal volume of vehicle. Inthe lenalidomide-CPI203 protocol, a total of 22 REC-1 tumor-bearing mice are randomly assigned to cohortsof 5-6 mice, receiving a twice daily intraperitoneal injection of 2.5 mg/kg CPI203, a daily intraperitonealinjection of 50 mg

13、/kg lenalidomide, both agents or an equal volume of vehicle. Between 26 and 29 days post-inoculation, animals are killed according to institutional guidelines and tumor samples are subjected toimmunohistochemical staining using primary antibodies against phospho-histone H3, cleaved caspase-3(5A1E) a

14、nd MYC (D84C12), IRF4 (M-17) and platelet endothelial cell adhesion molecule-1 (PECAM-1)(M20), CD19 (LE-CD19), Blimp-1 (clone Ros195G/G5), PAX5 (clone 24), CCL3 and CD38, as previouslydescribed. Preparations are evaluated using an Olympus DP70 microscope and Cell B Basic ImagingSoftware.MCE has not

15、independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Patent. US20180263995A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc NatlAcad Sci U S A. 2012 May 1;109(18):6927-32.2. Moros A, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantlecell lympho