TC-A2317 HYDROCHLORIDE

Biochem/physiol Actions

Orally active, potent and selective aurora A kinase inhibitor with anti-cancer activity in vitro and in vivo.

TC-A2317 (TC-A 2317) is an orally active, potent and selective aurora A kinase inhibitor (Ki = 1.2 nM; Aurora B Ki = 101 nM; IC50 >1 µM toward 60 other kinases). TC-A2317 inhibits the proliferation of human colorectal carcinoma HCT116 cells in cultures (IC50 = 115 nM) and suppresses HCT116 xenograft-derived tumor growth in mice in vivo (by 59% on day 14; 30 mg/kg/day p.o.) with good pharmacokinectic properties, oral bioavailability (T_max = 1.2 h, T1/2 = 3.3 h, C_max = 4930 nM, C60 min = 52 nM in rat serum post 30 mg/kg p.o.), and no adverse effects to the animals. TC-A231 is a racemate with its (S)-enantiomer being more active than the (R)-enantiomer (respective Ki = 0.59 vs. 66 nM).