AM-1882

AM-1882 is a potent and selective small molecule inhibitor of **KIF18A** (Kinesin Family Member 18A), a kinesin-8 motor protein that plays a critical role in regulating chromosome alignment during mitosis. KIF18A is considered a specific mitotic vulnerability in cancer cells exhibiting chromosomal instability (CIN+), as these cells depend on KIF18A to manage spindle tension and prevent lethal mitotic errors. By inhibiting KIF18A, AM-1882 induces G2/M cell-cycle arrest and suppresses the proliferation, migration, and invasion of CIN+ cancer cells. Preclinical research indicates that AM-1882 also triggers the **cGAS-STING** pathway and stimulates type I interferon (IFN) signaling, which promotes the activation of cytotoxic CD8+ T cells and reduces Treg proliferation. This shift in the tumor microenvironment enhances the efficacy of immune checkpoint blockades, such as PD-1 inhibitors, particularly in colorectal cancers with the CIN+ phenotype.