BAY-958

Description: BAY-958 is a lead compound for Atuveciclib (formerly known as BAY-1143572) which is novel, potent, oral and highly selective PTEFb/CDK9 inhibitor. It inhibits CDK9/CycT1 with an IC50 of 13 nM and is more than 100-fold more selective for CDK9 over CDK2. It also inhibits GSK3 kinase with IC50 values of 45 nM and 87 nM for GSK3alpha and GSK3beta respectively. Atuveciclib is currently in Phase I clinical trial. Selective inhibition of exclusively transcription-regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY-958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY?1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY?1143572 exhibited the best overall profile in?vitro and in?vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAY?1143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer.

References: ChemMedChem. 2017 Nov 8; 12(21):1776-1793.; Molecules. 2018, 23(5). pii: E1057.

Related CAS#:1414943-88-6 (BAY-1143572; Atuveciclib)