IAM-K1

IAM-K1 is a potent, brain-penetrant, allosteric small molecule inhibitor of KIF18A (Kinesin family member 18A). Developed by Iambic Therapeutics, IAM-K1 targets the spindle assembly checkpoint by dampening chromosome oscillation, which leads to cancer-specific dysregulation and cell death. KIF18A is a kinesin family motor protein that promotes chromosome alignment; its inhibition provides a therapeutic window by selectively affecting cancer cells with chromosomal instability. IAM-K1 has demonstrated low nanomolar potency in biochemical and cell-based assays and has shown superior activity compared to reference compounds like AMG650. Preclinical studies in OVCAR-3 xenograft models have shown durable tumor regression following oral administration without significant impact on body weight, suggesting a favorable safety profile and potential efficacy in treating solid tumors, including triple-negative breast cancer and ovarian cancer, as well as brain metastases.