AML874

AML874 is a potent and selective small molecule inhibitor of the Mediator complex, specifically targeting the CDK8 and CDK19 kinases. Developed by researchers at the Institute for Research in Immunology and Cancer (IRIC) and Hôpital Maisonneuve-Rosemont, it was identified through a high-throughput cell viability screen of primary acute myeloid leukemia (AML) specimens. AML874 disrupts Mediator complex structural integrity and function, leading to transcriptional dysregulation in leukemic cells. It has shown particular efficacy in FLT3-mutated AML subtypes and demonstrates strong synergistic anti-leukemic activity when combined with the BCL2 inhibitor venetoclax in both in vitro and in vivo xenograft models.