CCT251545

CCT251545 is a potent, selective, and orally bioavailable small molecule inhibitor of the Mediator complex-associated kinases CDK8 and CDK19. Discovered by the Institute of Cancer Research (ICR), the compound was developed to inhibit the Wnt/β-catenin signaling pathway and other transcriptional programs driven by the Mediator complex in various malignancies. CDK8 and CDK19 are part of the kinase module of the Mediator complex, which links specific transcription factors to the RNA polymerase II machinery. CCT251545 has demonstrated preclinical efficacy in models of colorectal cancer and acute myeloid leukemia (AML). In pediatric acute megakaryoblastic leukemia (AMKL), particularly those with the ETO2-GLIS2 fusion, research indicates that overexpression of MED12L may contribute to resistance against this inhibitor.