LY3295668 (AK-01) is a potent, orally active and specific inhibitor of Aurora A kinase with Ki of 0.8 nM and 1038 nM for AURKA and AURKB, respectively.
LY3295668, an AURKA inhibitor with over 1,000-fold selectivity versus AURKB, is distinguished by minimal toxicity to bone marrow cells at concentrations active against RB1mut cancer cells.[1]
LY3295668 leads to durable regression of RB1mut tumor xenografts at exposures that are well tolerated in rodents. Genetic suppression screens identifi ed enforcers of the spindle-assembly checkpoint (SAC) as essential for LY3295668 cytotoxicity in RB1-defi cient cancers and suggest a model in which a primed SAC creates a unique dependency on AURKA for mitotic exit and survival.[1]
[1] Xueqian Gong, et al. Cancer Discov. 2019 Feb;9(2):248-263.