AZ82

AZ82 is a potent and selective small molecule inhibitor of Kinesin Family Member C1 (KIFC1), also known as HSET. KIFC1 is a minus-end-directed microtubule motor protein that is essential for the survival of cancer cells with centrosome amplification. These cells rely on KIFC1 to cluster supernumerary centrosomes into two poles during mitosis, preventing multipolar spindle formation and subsequent mitotic catastrophe. AZ82 binds to the KIFC1-microtubule complex and inhibits its motor activity, thereby disrupting centrosome clustering. This leads to the formation of multipolar spindles, aneuploidy, and cell death specifically in cancer cells, while leaving normal cells (which typically have only two centrosomes) unaffected. In melanoma research, AZ82 has demonstrated the ability to significantly reduce cell growth and alter the expression of genes involved in the G2M checkpoint and MYC signaling pathways.