CRFR1拮抗剂CP-154526的脱靶作用

Off-target effects of corticotropin releasing factor receptor 1 antagonist CP-154526

目的:CP-154526是选择性促肾上腺皮质激素释放激素1型受体(CRFR1)拮抗剂,但其脱靶作用仍未阐述清晰。方法:本研究以CP-154526为研究对象,以化合物-蛋白相互组学为手段,构建其药物-药物网络并做数据挖掘。结果:DRAR-CPI实验结果显示CP-154526与23个药物相似,与抗肿瘤药物和抗感染药物相似较多,与治疗帕金森病Bromocripti最为相似。数据挖掘进一步分析发现CP-154526可与单胺氧化酶B有作用。结论:CP-154526可能具有抗肿瘤、抗感染等多方面脱靶作用,还可能通过单胺氧化酶B治疗帕金森病症。本研究为快速评价药物的全面疗效提供一种思路。

OBJECTIVE CP-154526 is a selective antagonist of corticotropin releasing factor receptor type 1.However,its off-target effects still remain obscure.METHODS In this study,drug-drug network for CP-154526 was constructed using chemical-protein interactome（CPI）and checked by data mining.RESULTS DRAR-CPI results showed that CP-154526 was similar with 23 drugs,of which 6 were related with anti-cancer,3 with anti-infective.Bromocripti for Parkinson＇s Disease was most similar to CP-154526.Moreover,amine oxidase B might be a target of CP-154526 for Parkinson＇s Disease by data mining.CONCLUSION CP-154526 shows various off-targets effects,including anti-cancer,anti-infective,etc.,and may benefit Parkinson＇s Disease by MAO B.This study may provide a way to quickly evaluate drug efficacy.