1094067-13-6

中文名称:

1094067-13-6

中文同义词:

AURORA A和AURORA B抑制剂(SCH-1473759 HYDROCHLORIDE)

英文名称:

SCH1473759 (HCl salt)

英文同义词:

SCH1473759 (HCl salt);SCH-1473759 hydrochloride;SCH-1473759 HCl

CAS号:

1094067-13-6

分子式:

分子量:

0

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

Mol File

生物活性

SCH-1473759 hydrochloride是多靶点的的极光激酶 (aurora) 抑制剂，对极光激酶A和B的IC50 值分别为4 和13 nM。

靶点

Aurora A 4 nM (IC 50 ) Aurora B 13 nM (IC 50 )

Aurora A 4 nM (IC 50 )

Aurora B 13 nM (IC 50 )

体外研究

SCH-1473759 directly binds to aurora A and B with K d s of 20 and 30 nM, respectively. SCH-1473759 also inhibits the Src family of kinases (IC 50 <10 nM), Chk1 (IC 50 =13 nM), VEGFR2 (IC 50 =1 nM), and IRAK4 (IC 50 =37 nM). It does not have significant activity (IC 50 >1000 nM) against 34 other kinases representing different families of the kinome. SCH-1473759 inhibits HCT116 cells proliferation with an IC 50 of 6 nM. SCH 1473759 inhibits tumor cell lines from different tissues (breast, ovarian, prostate, lung, colon, brain, gastric, renal, skin, and leukemia). The most sensitive cell lines includ A2780, LNCap, N87, Molt4, K562, and CCRF-CEM with IC 50 values <5 nM.

体内研究

SCH-1473759 at a low dose of 5 mg/kg (ip, 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(ip, bid) is well-tolerated in an intermittent schedule (5 days on, 5 days off) and gave 69% TGI on day 16. SCH-1473759 shows good exposure in all species with the clearance being high in rodents and moderate in dog and monkey. The half-life is also moderate, but the tissue distribution is high. 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.