CC-671 is a dual inhibitor of TTK protein kinase (IC50: 0.005 μM) and CLK2 (IC50: 0.006 μM).

TTK:0.005 μM, CLK2:0.006 μM

HCT-116 cell lysates treated with CC-671 at 3 μM for 1 h demonstrates that only four kinases show cellular binding of 75% or more including CLK2, CAMKK2, PIP4K22, and JNK[1].

CC-671 significantly inhibits tumor growth by 71% at doses of both 10 and 20 mg/kg on an every 3 days (q3d) dosing schedule, with no difference in efficacy between the two doses. However, it induces greater body weight loss at 20 mg/kg compared to 10 mg/kg (17% vs 5%)[1].

The kinase selectivity profile of CC-671 is assessed. The screen is conducted with the concentration of CC-671 held constant at 3 μM. The TTK binding affinity is measured using the kinase binding assays. The kinase binding assays are based on the binding and displacement of a proprietary, Alexa Fluor 647-labeled, ATP-competitive kinase inhibitor scaffold[1].

Female SCID mice are inoculated subcutaneously with 5×106 Cal-51 cells. Mice with tumours of approximately 125 mm3 are randomized and treated intravenously at various doses and schedules of CC-671 (n=8 to10/group). Tumours are measured twice a week for the duration of the study. The long and short axes of each a tumour are measured using a digital calliper in millimetres and the tumour volumes are calculated[1].