BAY-1143572.

Uses

Atuveciclib Racemate (BAY-1143572 Racemate) is the racemate mixture of Atuveciclib. Atuveciclib is a potent and highly selective, oral P-TEFb/CDK9 inhibitor which supresses CDK9/CycT1 with an IC50 of 13 nM.

Biological Activity

Atuveciclib (BAY-1143572) is a potent and highly selective PTEFb/CDK9 inhibitor with IC50 of 13 nM for CDK9/CycT. Its IC50 for CDK2 is about 100-fold higher than that for CDK9. In addition to CDK family members, it also inhibits GSK3 kinase with IC50 values of 45 nM and 87 nM for GSK3α and GSK3β, respectively.

in vivo

BAY 1143572 has a low plasma clearance (CL _b 1.1 L/h/kg) and a volume of distribution (Vss) of 1.0 L/kg in a rat pharmacokinetic study . Its oral bioavailability is 54% and the blood-plasma concentration ratio is 1. BAY 1143572 has no significant inhibitory effect on cytochrome P450 activity, IC50>20 μM. NOD/Shi-scid/IL-2Rγ in immunocompromised.

target

IC 50

CDK9

References

[1] Scholz A, et al. BAY 1143572, a first-in-class, highly selective, potent and orally available inhibitor of PTEFb/CDK9 currently in Phase I, shows convincing anti-tumor activity in preclinical models of acute myeloid leukemia (AML). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3022.
[2] Scholz A, et al. BAY 1143572: A first-in-class, highly selective, potent and orally available inhibitor of PTEFb/CDK9 currently in Phase I, inhibits MYC and shows convincing anti-tumor activity in multiple xenograft models by the induction of apoptosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr DDT02-02. doi:10.1158/1538-7445.AM2015-DDT02-02