CCT244747

CCT244747 is a potent inhibitor of checkpoint kinase 1 (Chk1, IC50 = 8 nM). It is selective for Chk1 over FLT3, Chk2, and CDK1 (IC50s = 600, >10,000, and >10,000 nM, respectively) as well as a panel of 121 additional kinases at a concentration of 10 µM. CCT244747 reverses cell cycle arrest at the G2/M phase induced by etoposide (Cay-12092) and SN-38 (Cay-15632) in HT-29 cells and gemcitabine (Cay-11690, Cay-9003096) in SW620 cells, indicating cellular G2 checkpoint abrogation. It potentiates the genotoxicity of SN-38, gemcitabine, and etoposide in HT-29, SW620, MiaPaCa-2, and Calu-6 cells with potentiation index (PI) values ranging from 1.9-8.5, 2.6-12.2, 5-16, and 1.4-5.6, respectively. In vivo, CCT244747 (75 mg/kg), in combination with irinotecan (Cay-14180) or gemcitabine, increases the delay of tumor growth in SW620 and Calu-6 mouse xenograft models, respectively.Formal Name: 3-[(1R)-2-(dimethylamino)-1-methylethoxy]-5-[[4-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]amino]-2-pyrazinecarbonitrile. CAS Number: 1404095-34-6. Molecular Formula: C20H24N8O2. Formula Weight: 408.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. SMILES: COC1=C(C2=CN(C)N=C2)C=NC(NC3=CN=C(C#N)C(O[C@H](C)CN(C)C)=N3)=C1. InChi Code: InChI=1S/C20H24N8O2/c1-13(11-27(2)3)30-20-16(7-21)22-10-19(26-20)25-18-6-17(29-5)15(9-23-18)14-8-24-28(4)12-14/h6,8-10,12-13H,11H2,1-5H3,(H,23,25,26)/t13-/m1/s1. InChi Key: IENLGMOXAQMNEH-CYBMUJFWSA-N.