Atuveciclib(BAY-1143572)是一种有效的，具有口服活性的高选择性PTEFb/CDK9抑制剂。Atuveciclib(BAY-1143572)抑制CDK9/CycT1，IC50为13nM。
Atuveciclib (BAY-1143572) is a potent and highly selective, oral PTEFb/CDK9 inhibitor. Atuveciclib (BAY-1143572) inhibits CDK9/CycT1 with an IC50 of 13 nM[1].
Positive transcription elongation factor b (PTEFb) is a heterodimer of CDK9 and one of four cyclin partners, cyclin T1, cyclin K, cyclin T2a or cyclin T2b. Atuveciclib (BAY-1143572) demonstrates potent antiproliferative activity against HeLa cells (IC50=920 nM) and MOLM-13 cells (IC50=310 nM)[1].
In vivo efficacy studies in the MOLM-13 xenograft model in mice, Atuveciclib (BAY-1143572) demonstrates great potency and high antitumor efficacy. Daily administration of Atuveciclib (BAY-1143572) at 6.25 or 12.5 mg/kg results in a dose-dependent antitumor efficacy with a treatment-to-control (T/C) ratio of 0.64 and 0.49, respectively (p<0.001). In a separate experiment with a higher daily dose of 20 or 25 mg/kg Atuveciclib (BAY-1143572), antitumor efficacy with a T/C ratio of 0.41 and 0.31, respectively, is observed (p<0.001). The 25 mg/kg once daily dose is the maximum tolerated dose in nude mice. Furthermore, Atuveciclib (BAY-1143572) administered at 25 or 35 mg/kg, three days on / two days off, results in a T/C ratio of 0.33 and 0.20, respectively (p<0.001). Treatment with Atuveciclib (BAY-1143572) is well-tolerated, as demonstrated by less than 10 % mean body weight reduction throughout the study. In an in vivo pharmacokinetic study in rats, Atuveciclib (BAY-1143572) shows low blood clearance (CLb 1.1 L/kg per hour)[1].
[1]. Lücking U, et al. Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer. ChemMedChem. 2017 Nov 8;12(21):1776-1793.
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