Ocifisertib (fumarate)

CFI-400945 fumarate is a potent, selective and orally bioavailable PLK4 inhibitor with a K_i and an IC₅₀ of 0.26 nM and 2.8 nM, respectively. IC50 & Target:Ki: 0.26 nM (PLK4)^[1]
IC50: 2.8 nM (PLK4)^[1] In Vitro: CFI-400945 (compound 48) shows potent inhibitory activities against a panel of kinases, including PLK4, TRKA, TRKB, AURKA, AURKB/INCENP, and TIE2/TEK, with IC₅₀s of 2.8, 6, 9, 140, 98, 22 nM, and EC₅₀s of 12, 84, 88, 510, 102, 117 nM, respectively. CFI-400945 exhibits growth inhibition effects on breast, lung, ovarian and colon cancer cells. The IC₅₀s (in μM) are as follows: SKBr-3 (5.3), Cal-51 (0.26), BT-20 (0.058), A549 (0.005), OVCAR-3 (0.018), SW620 (0.38), Colo-205 (0.017), and HCT116+/+ (0.004) ^[1]. CFI-400945 inhibits autophosphorylation of PLK4 at serine 305 with an EC₅₀ value of 12.3 nM in cells overexpressing PLK4. Cancer cells treated with CFI-400945 exhibit effects consistent with PLK4 kinase inhibition, including dysregulated centriole duplication, mitotic defects, and cell death^[2]. In Vivo: Oral administration of CFI-400945 (3.0, 9.4 mg/kg) to mice bearing human cancer xenografts results in the significant inhibition of tumor growth at doses that are well tolerated. Increased antitumor activity is observed in PTEN-deficient compared to PTEN wild-type cancer xenografts. The maximum tolerated dose for once-daily administration of CFI-400945 is estimated to be 7.5-9.5 mg/kg^[2].