CFI-400945 is an orally active, potent, and selective inhibitor of polo-like kinase 4.

TRKB:9 nM, AURKB/INCENP:98 nM, TIE2/TEK:22 nM, AURKA:140 nM, PLK4:2.8 nM, TRKA:6 nM

In an assay using recombinant human PLK4, CFI-400945 inhibited PLK4 (IC50: 2.8 ± 1.4 nM and Ki: 0.26 ± 0.1 nM in an ATP competitive manner). CFI-400945 inhibited autophosphorylation of PLK4 at serine 305 (EC50: 12.3 nM in cells overexpressing PLK4). CFI-400945 showed no significant inhibitory activity against other PLK family members (PLK1, PLK2, and PLK3 with the IC50s of > 50 μM). In transfected HCT116 cells with TRKA, TRKB, and Tie2/TEK, the EC50 values were 84 nM, 88 nM, and 117 nM, respectively. CFI-400945 inhibited the activity of AURKA and AURKB with the EC50 value of 510 nM and 102 nM. CFI-400945 (≥ 200 nM) decreased the mean centriole number in asynchronous U2OS cells. CFI-400945 inhibited a panel of breast cancer cell growth with the GI50 of 14-165 nM [1].

In mice, the maximum tolerated dose (MTD) of CFI-400945 for once-daily oral administration was estimated to be 7.5-9.5 mg/kg [1].