Design, synthesis, and biological evaluation of indazole-based PLK4 inhibitors.

ABSTRACT: Polo-like kinase 4 (PLK4), a member of the serine/threonine protein kinase family, serves as a central regulator of centriole duplication and plays a critical role in eukaryotic mitosis. Overexpression of PLK4 in several cancer types underscores its potential as a therapeutic target. In our previous studies, compound 28t demonstrated acceptable kinase inhibitory activity but exhibited poor cellular activity. Consequently, 28t was selected as a lead compound for further optimization. Through functional group migration and rational drug design strategies, we conducted structural modifications that ultimately yielded 23 novel indazole-based PLK4 inhibitors. Among these, compound C05 exhibited exceptional kinase inhibitory activity (IC₅₀ < 0.1 nM). At the cellular level, C05 demonst

SUBMITTER: Fan C 

PROVIDER: S-EPMC12499891 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature