BAY-1143572 Racemate

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

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Research Areas >> Cancer

CDK9

BAY 1143572 inhibits the proliferation of 7 MLL-rearrangements positive and negative AML cell lines with a median IC50 of 385 nM (range 230-1100 nM) and induces apoptosis[1]. BAY 1143572 has potent and highly selective PTEFb-kinase inhibitory activity in the low nanomolar range against PTEFb/CDK9 and an at least 50-fold selectivity against other CDKs. BAY 1143572 shows a favorable selectivity against a panel of non-CDK kinases. It shows broad antiproliferative activity against a panel of tumor cell lines with sub-micromolar IC50 values. The concentration-dependent inhibition of the phosphorylation of the RNA polymerase II and downstream reduction of MYC mRNA and protein levels is observed[2].

BAY 1143572 exhibits single agent efficacy at tolerated doses in 4 out of 5 AML xenograft tumor models in mice and in 2 out of 2 AML xenograft tumor models in rats upon once daily oral administration. Partial or even complete remissions could be achieved in several models[1].The inhibition of MYC mRNA is also observed in blood cells of BAY 1143572-treated rats indicating the potential clinical utility of MYC in blood cells as a pharmacodynamic marker in clinical development. The in vivo efficacy of BAY 1143572 is significantly enhanced in combination with several chemotherapeutics in different solid tumor models[2].

[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

Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | THZ531 | RO-3306 | Flavopiridol | NVP 2 | CYC-065 | AZD5438 | BIO | Kenpaullone | SNS-032 (BMS-387032) | CDK9-IN-2