Simurosertib

Simurosertib is an inhibitor of cell division cycle 7 (Cdc7) kinase (IC50 = 0.26 nM). It is selective for Cdc7 over cyclin-dependent kinase 2 (Cdk2) and Rho-associated kinase 1 (ROCK1, IC50s = 6,300 and 430 nM, respectively). It inhibits phosphorylation of DNA replication licensing factor MCM2 in HeLa cells (IC50 = 17 nM) and reduces proliferation of COLO 205 cells (EC50 = 81 nM). Simurosertib induces replication stress, halts the cell cycle at the G2/S phase, and inhibits the growth of a wide variety of cancer cells (GI50s = 30.2->10,000 nM). It reduces intratumor levels of phosphorylated MCM2 in COLO 205 and SW948 mouse xenograft models when administered at a dose of 80 mg/kg and reduces tumor growth in the same models when administered at doses of 40 or 60 mg/kg twice per day.Formal Name: 2-(2S)-1-azabicyclo[2.2.2]oct-2-yl-6-(3-methyl-1H-pyrazol-4-yl)-thieno[3,2-d]pyrimidin-4(3H)-one. CAS Number: 1330782-76-7. Synonyms: TAK-931. Molecular Formula: C17H19N5OS. Formula Weight: 341.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. SMILES: O=C1N=C(NC2=C1SC(C3=CNN=C3C)=C2)[C@@]4([H])N5CCC(CC5)C4. InChi Code: InChI=1S/C17H19N5OS/c1-9-11(8-18-21-9)14-7-12-15(24-14)17(23)20-16(19-12)13-6-10-2-4-22(13)5-3-10/h7-8,10,13H,2-6H2,1H3,(H,18,21)(H,19,20,23)/t13-/m0/s1. InChi Key: XGVXKJKTISMIOW-ZDUSSCGKSA-N.