SCH-1473759 is an inhibitor of the aurora (IC50s: 4 and 13 nM for Aurora A and B, respectively).

Aurora A:4 nM, Aurora B:13 nM

SCH-1473759 inhibits HCT116 cells proliferation (IC50: 6 nM). SCH 1473759 inhibits tumor cell lines from different tissues (breast, ovarian, prostate, lung, colon, brain, gastric, renal, skin, and leukemia). SCH-1473759 also inhibits the Src family of kinases (IC50<10 nM), Chk1 (IC50=13 nM), VEGFR2 (IC50=1 nM), and IRAK4 (IC50=37 nM). SCH-1473759 directly binds to aurora A and B with Kds of 20 and 30 nM, respectively. It does not have significant activity (IC50>1000 nM) against 34 other kinases representing different families of the kinome. The most sensitive cell lines include A2780, LNCap, N87, Molt4, K562, and CCRF-CEM with IC50 values <5 nM [1][2].

SCH-1473759 shows good exposure in all species with the clearance being high in rodents and moderate in dog and monkey. SCH 1473759 dose- and schedule-dependent anti-tumor activity in four human tumor xenograft models. SCH-1473759 at a low dose of 5 mg/kg (i.p., bid) is well-tolerated in a continuous dosing schedule and shows 50% tumor growth inhibition(TGI) on day 16. A higher dose of 10mg/kg(i.p., bid) is well-tolerated in an intermittent schedule (5 days on, 5 days off) and gave 69% TGI on day 16. The half-life is also moderate, but tissue distribution is high [1][2].