Orally Bioavailable 4-Phenoxy-quinoline Compound as a Potent Aurora Kinase B Relocation Blocker for Cancer Treatment.

ABSTRACT: We investigated a novel 4-phenoxy-quinoline-based scaffold that mislocalizes the essential mitotic kinase, Aurora kinase B (AURKB). Here, we evaluated the impact of halogen substitutions (F, Cl, Br, and I) on this scaffold with respect to various drug parameters. Br-substituted LXY18 was found to be a potent and orally bioavailable disruptor of cell division, at sub-nanomolar concentrations. LXY18 prevents cytokinesis by blocking AURKB relocalization in mitosis and exhibits broad-spectrum antimitotic activity in vitro. With a favorable pharmacokinetic profile, it shows widespread tissue distribution including the blood-brain barrier penetrance and effective accumulation in tumor tissues. More importantly, it markedly suppresses tumor growth. The novel mode of action of LXY

SUBMITTER: Li J 

PROVIDER: S-EPMC10425991 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature