Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination.

ABSTRACT:

Background

Threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) are common essential kinases that collaborate in activating the spindle assembly checkpoint (SAC) at the kinetochore, ensuring appropriate chromosome alignment and segregation prior to mitotic exit. Targeting of either TTK or PLK1 has been clinically evaluated in cancer patients; however, dual inhibitors have not yet been pursued. Here we present the in vitro and in vivo characterization of a first in class, dual TTK/PLK1 inhibitor (BAL0891).

Methods

Mechanism of action studies utilized biochemical kinase and proteomics-based target-engagement assays. Cellular end-point assays included immunoblot- and flow cytometry-based cell cycle analyses and SAC integrity evaluation using immunoprecipi

SUBMITTER: Zanini E 

PROVIDER: S-EPMC11341980 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature