RCZY-843

RCZY-843 is a potent, orally bioavailable, second-generation small molecule inhibitor of the menin-MLL (KMT2A) interaction. Developed by Rongchang Pharmaceuticals and RemeGen, it is specifically engineered to overcome clinical resistance mediated by MEN1 somatic mutations (such as M327I/V, G331R, and T349M) that have been observed with first-generation menin inhibitors like revumenib and ziftomenib. By disrupting the menin-MLL1 complex, RCZY-843 inhibits the expression of leukemogenic drivers including HOXA and MEIS1. In preclinical models of KMT2A-rearranged and NPM1-mutant acute myeloid leukemia (AML), RCZY-843 has demonstrated superior binding affinity, enhanced pharmacokinetics, and greater tumor growth inhibition compared to earlier clinical-stage inhibitors, suggesting potential as a best-in-class therapeutic for resistant acute leukemias.