6K465

6K465 is a novel, pyrimidine-based small molecule inhibitor of Aurora kinase A (AURKA). It is designed to treat MYC-amplified solid tumors by destabilizing c-MYC and N-MYC oncoproteins, which are often overexpressed in aggressive cancers. Compared to the AURKA inhibitor alisertib, 6K465 demonstrates more potent reduction of MYC levels and possesses a uniquely long tumor half-life. An acyl-based prodrug, DBPR728, has been developed to improve the oral bioavailability of 6K465. Preclinical studies have shown that 6K465 (administered via its prodrug) induces durable tumor regression in xenograft models of small cell lung cancer (SCLC), triple-negative breast cancer (TNBC), hepatocellular carcinoma, and medulloblastoma. It also shows synergistic effects when combined with the mTOR inhibitor everolimus.