AM-9022

AM-9022 is a potent and selective small-molecule allosteric inhibitor of the kinesin motor protein KIF18A, developed by Amgen. It specifically targets the microtubule-associated ATPase activity of KIF18A by binding to an allosteric pocket formed by motor helices α4 and α6, near the microtubule-binding surface. By inhibiting KIF18A, the drug induces mitotic arrest, spindle assembly checkpoint (SAC) activation, centrosome fragmentation, and subsequent apoptosis in chromosomally unstable (CIN) cancer cells, particularly those with TP53 mutations. AM-9022 has demonstrated significant anti-tumor activity, including tumor regression, in preclinical models of high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC). As an oral candidate, it is designed for high bioavailability and low clearance, exhibiting a favorable safety profile that spares normal proliferating cells such as bone marrow and sensory neurons.