Atuveciclib (BAY-1143572) is a potent and highly selective oral PTEFb/CDK9 inhibitor, demonstrating an IC50 of 13 nM in inhibiting CDK9/CycT1.

CDK3-CyclinE:890 nM, CDK2-CyclinE:1000 nM, CDK1-CyclinB:1100 nM, CDK9-CyclinT1:13 nM, CDK9-CyclinT1:6 nM, CDK5-p35:1600 nM

Positive transcription elongation factor b (PTEFb), consisting of a CDK9-cyclin heterodimer with cyclin T1, cyclin K, cyclin T2a, or cyclin T2b, shows notable antiproliferative effects on HeLa cells (IC 50 = 920 nM) and MOLM-13 cells (IC 50 = 310 nM) when targeted with Atuveciclib (BAY-1143572) [1].

In vivo studies using the MOLM-13 xenograft mouse model show that Atuveciclib (BAY-1143572) demonstrates significant antitumor activity. Administering Atuveciclib daily at doses of 6.25 or 12.5 mg/kg leads to dose-dependent tumor suppression, with treatment-to-control (T/C) ratios of 0.64 and 0.49, respectively (p<0.001). Higher doses of 20 or 25 mg/kg result in even stronger antitumor effects, with T/C ratios dropping to 0.41 and 0.31, respectively (p<0.001), and the 25 mg/kg dose being the highest tolerated by the nude mice. Additionally, dosing Atuveciclib at 25 or 35 mg/kg on a schedule of three days on and two days off yields T/C ratios of 0.33 and 0.20, respectively (p<0.001). The compound's tolerability is confirmed by a less than 10% average reduction in body weight throughout the study period. Pharmacokinetic evaluation in rats reveals Atuveciclib has a low blood clearance rate of 1.1 L/kg per hour.