AM-5308

AM-5308 is a potent and selective small-molecule inhibitor of the kinesin motor protein KIF18A, developed by Amgen. It is designed to target cancers characterized by chromosomal instability (CIN), such as high-grade serous ovarian cancer (HGSOC) and triple-negative breast cancer (TNBC). By inhibiting KIF18A, the drug induces mitotic arrest, spindle assembly checkpoint (SAC) activation, and subsequent apoptosis specifically in chromosomally unstable cancer cells, while sparing normal somatic cells. Preclinical studies demonstrate that AM-5308 leads to tumor regression in TP53-mutant HGSOC and TNBC models at well-tolerated doses. It functions as an allosteric inhibitor that is non-competitive with ATP and microtubules.