| 产品描述： | CDK9 选择性抑制剂;CDK9 Selective Inhibitors;;InformationAtuveciclib (BAY-1143572) is potent and highly selectivePTEFb/CDK9inhibitor withIC50values of 13 nM for CDK9/CycT and the ratio of IC50 values for CDK2/CDK9 is about 100. Outside the CDK family, It inhibits GSK3 kinase with IC50 values of 45 nM and 87 nM for GSK3α and GSK3β respectively.TargetsCDK9 (Cell-free assay); GSK-3α ; GSK3β 13 nM; 45 nM; 87 nMIn vitroBAY\u20051143572 is a potent and highly selective CDK9 inhibitor (IC50 CDK9/CycT1: 13\u2005nM, ratio of IC50 values CDK2/CDK9: 100). Outside the CDK family, submicromolar inhibitory activity was only recorded against GSK3 kinase (IC50 GSK3α: 45\u2005nM, GSK3β: 87\u2005nM). BAY\u20051143572 demonstrates antiproliferative activity against HeLa cells (IC50 = 920\u2005nM) and MOLM-13 cells (IC50 = 310\u2005nM). It also demonstrates improved Caco-2 permeability and a decreased efflux ratio (PappA→B: 35\u2005nm/s, ER: 6) relative to lead compound BAY‐958 (PappA→B: 22\u2005nm/s, ER: 15). In vivoIn an in\u2005vivo pharmacokinetic study in rats, BAY\u20051143572 showed low blood clearance (CLb 1.1\u2005L/h/kg). The volumes of distribution (Vss) of BAY\u20051143572 is 1.0\u2005L/kg. BAY\u20051143572 shows significantly improved oral bioavailability of 54\u2009%. The blood/plasma ratios is about 1. It does not show significant inhibition of cytochrome P450 activity, with IC50 values >20\u2005μM. The administration of BAY 1143572 in immunocompromized NOD/Shi-scid/IL-2Rγ (NOG) mice xenografted with patient-derived ATL cells greatly reduced the infiltration of ATL cells into organs, such as liver and bone marrow. Decreased human soluble IL2R levels in serum were also observed, which indicated a reduction of ATL tumor burden. |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京