SCH-1473759 hydrochloride is an inhibitor of aurora(aurora A and B with IC50s of 4 and 13 nM, respectively).

Aurora A:4 nM, Aurora B:13 nM

SCH-1473759 directly binds to aurora A and B (Kds of 20 and 30 nM, respectively) and inhibits the Src family of kinases (IC50 less than 10 nM), Chk1 (IC50 of 13 nM), VEGFR2 (IC50 of 1 nM), and IRAK4 (IC50 of 37 nM). It inhibits tumor cell lines from various tissues, including breast, ovarian, prostate, lung, colon, brain, gastric, renal, skin, and leukemia. The most sensitive cell lines include A2780, LNCap, N87, Molt4, K562, and CCRF-CEM with IC50 values <5 nM [2].

SCH-1473759(5 mg/kg ,ip, bid) was well tolerated in the continuous dosing regimen and showed 50% tumor growth inhibition (TGI) on day 16. SCH-1473759(10mg/kg,ip, bid) is well-tolerated in an intermittent schedule (5 days on, 5 days off) and gave 69% TGI on day 16. SCH-1473759 showed good exposure in all species, with high clearance rates in rodents and moderate clearance rates in dogs and monkeys.The half-life is also moderate, but the tissue distribution is high[1]. SCH 1473759 dose- and schedule-dependent anti-tumor activity in four human tumor xenograft models. Further, the efficacy is enhanced in combination with taxanes and found to be most efficacious when SCH 1473759 is dosed 12-h post-taxane treatment[2].