Synthesis and structure-activity relationships of targeted protein degraders for the understudied kinase NEK9.

ABSTRACT: Nek9 is a member of the understudied Nek family of dark kinases. Aberrant activation of Nek9 kinase signaling has been linked to poor keratinocyte differentiation phenotypes, and is a key driver of nevus comedonicus, a rare, localized form of acne. Nek9 also has essential scaffolding roles; during mitosis the non-catalytic C-terminal domain of Nek9 binds to Nek6 and Nek7, releasing them from an auto-inhibitory conformation, and enabling proper mitotic progression. Finally, Nek9 expression has been linked to cancer proliferation. SiRNA mediated Nek9 knock-down in a panel of cancer cell lines induces G1 cell cycle arrest and inhibits proliferation when p53 is also inactivated; cell lines with functional p53 are unaffected. Presently, no selective small molecule Nek9 chemical probes are avail

SUBMITTER: Ryu S 

PROVIDER: S-EPMC12364016 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature