MC180295

MC180295 is a novel, highly selective small molecule inhibitor of cyclin-dependent kinase 9 (CDK9). CDK9 is a critical component of the positive transcription elongation factor b (P-TEFb) complex, which regulates transcription elongation and mRNA maturation by phosphorylating RNA polymerase II (RNAP2) at Serine 2. By inhibiting CDK9, MC180295 downregulates the transcription and protein levels of key oncogenic drivers and anti-apoptotic factors, including MYC, MCL-1, cyclin D1, and BCL-XL. In preclinical studies, MC180295 has demonstrated potent anti-cancer activity in mantle cell lymphoma (MCL) models, including those resistant to ibrutinib and venetoclax. It has also shown synergistic effects when combined with venetoclax. The compound was developed through research collaboration involving the University of Texas Medical Branch and MD Anderson Cancer Center.