Design, synthesis, and biological evaluation of novel pyrimidin-2-amine derivatives as potent PLK4 inhibitors.

ABSTRACT: Serine/threonine protein kinase PLK4 is a master regulator of centriole duplication, which is significant for maintaining genome integrity. Accordingly, due to the detection of PLK4 overexpression in a variety of cancers, PLK4 has been identified as a candidate anticancer target. Thus, it is a very meaningful to find effective and safe PLK4 inhibitors for the treatment of cancer. However, the reported PLK4 inhibitors are scarce and have potential safety issues. In this study, a series of novel and potent PLK4 inhibitors with an aminopyrimidine core was obtained utilizing the scaffold hopping strategy. The in vitro enzyme activity results showed that compound 8h (PLK4 IC₅₀ = 0.0067 μM) displayed high PLK4 inhibitory activity. In addition, compound 8h exhibited a good plasm

SUBMITTER: Xue Y 

PROVIDER: S-EPMC10507801 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature