抗肿瘤候选药物SPH0396与乳腺癌耐药蛋白的关系研究  

Interactions of anti-tumor candidate SPH0396 with breast cancer resistance protein

作　　者：徐佳[1] 毛煜[1] 

机构地区：[1]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《上海医药》2017年第15期83-87,94,共6页Shanghai Medical & Pharmaceutical Journal

摘　　要：目的 :评价SPH0396与乳腺癌耐药蛋白(BCRP)的关系,从而推测其在临床上与其底物或抑制剂合用时发生药物-药物相互作用的可能性,为临床研究提供参考。方法 :采用Caco-2细胞模型,测定SPH0396(1μmol/L)的校正外排比(corrected efflux ratio,CER),并且以E3S为底物时1μmol/L和5μmol/L的SPH0396对BCRP的抑制率。结果 :SPH0396的校正外排比为1.33,对BCRP的抑制率不到阳性抑制剂KO143的50%。结论 :SPH0396不是BCRP潜在底物和抑制剂,因此SPH0396与BCRP的底物和抑制剂发生药物-药物相互作用的可能性很低。Objective： To evaluate the interactions of anti-tumor candidate SPH0396 with breast cancer resistance protein （BCRP）, and its potential drug-drug interaction （DDI） with BCRP substrates or inhibitors in clinic, which can provide a reference for clinical drug-drug interaction study. Methods： Caco-2 cells in vitro were used throughout the experiment to determine the corrected efflux ratio of SPH0396 at 1 μmol/L and the inhibition rate of SPH0396 at 1 μmol/L and 5 μmol/L when estrone-3-sulfate was used as a substrate. Results： The corrected efflux rate of SPH0396 was 1.33. The inhibitory rate of SPH0396 on BCRP was less than 50% of KO143 positive inhibitors. Conclusion： The present studies demonstrate that SPH0396 may be neither a substrate nor an inhibitor for BCRP, and have low potential to cause drug-drug interactions with BCRP substrate drugs.

关 键 词：酪氨酸激酶抑制剂 乳腺癌耐药蛋白 药物-药物相互作用 

分 类 号：R96[医药卫生—药理学]