Luvixasertib (hydrochloride)

CFI-402257 hydrochloride is a highly selective and orally bioavailable TTK/Mps1 inhibitor with an IC₅₀ of 1.7 nM for TTK in vitro. CFI-402257 hydrochloride has anti-cancer activity^[1]. IC50 & Target:IC50: 1.7 nM (TTK in vitro)^[1]. In Vitro: CFI-402257 is highly selective to TTK. CFI-402257 is tested against a panel of human kinases at 1 μM and inhibits none of the 262 kinases tested. CFI-402257 is a potent inhibitor of cell growth^[1].
CFI-402257 (200 nM, 6 h) causes a massive increase in chromosome missegregations^[2].
CFI-402257 (0, 50 or 100 nM) induces a dose-dependent dysregulation of the cell cycle, resulting in an increase in the frequency of cells exhibiting an aneuploid DNA content^[2].
CFI-402257 exhibits effects consistent with Mps1 kinase inhibition, specifically SAC inactivation, leading to chromosome missegregation, aneuploidy, and ultimately cell death^[2]. In Vivo: CFI-402257 given orally QD shows dose-dependent activity in mice with established tumors from xenografted MDA-MB-231 human TNBC cells and MDA-MB-468 human TNBC cells in mice. CFI-402257 demonstrates antitumor activity in a platinum-resistant PDX model of high-grade serous ovarian cancer^[2].