CFI-402257 hydrochloride, a highly selective and orally bioavailable inhibitor targeting TTK/Mps1, demonstrates an in vitro IC50 value of 1.7 nM against TTK. This compound exhibits anti-cancer activity [1].

CFI-402257 exhibits high specificity towards TTK, showing no inhibitory activity against a broad range of 262 human kinases at a concentration of 1 μM. It is a potent inhibitor of cell growth, as evidenced in various studies. At a concentration of 200 nM for 6 hours, it significantly increases chromosome missegregations. Furthermore, it induces a dose-dependent disruption of the cell cycle at concentrations of 0, 50, or 100 nM, increasing the prevalence of aneuploid DNA content in cells. These effects align with those expected from Mps1 kinase inhibition, such as SAC inactivation, leading to chromosome missegregation, aneuploidy, and ultimately, cell death.

Administered orally on a daily basis, CFI-402257 exhibits dose-dependent efficacy in targeting established tumors in mice, derived from xenografted MDA-MB-231 and MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Furthermore, CFI-402257 has shown to possess significant antitumor capabilities in a patient-derived xenograft (PDX) model of platinum-resistant high-grade serous ovarian cancer.