(1E)-CFI-400437 dihydrochloride is a potent PLK4 (IC50= 0.6 nM) inhibitor and selective against other members of the PLK family (>10 μM). (1E)-CFI-400437 dihydrochloride inhibits Aurora A, Aurora B, KDR and FLT-3 with IC50s of 0.37, 0.21, 0.48, and 0.18 μM, respectively. Antiproliferative activity.In Vivo: (1E)-CFI-400437 (25 mg/kg; intraperitoneal injection; daily for 21 days) dihydrochloride shows effective in a mouse xenograft model of tumor growth.
The plasma levels of (1E)-CFI-400437 (50 mg/kg; IP; mice) dihydrochloride shows a Cmax of 92 ng/mL and AUC of 190 ng?h/mL, respectively. The mouse plasma protein binding measurement for (1E)-CFI-400437 is 99%, i.e., unbound compound in plasma is 1%.