基于分子对接技术的血小板P2Y_(12)受体拮抗剂研究现状

Current Researches of Platelet P2Y_(12) Receptor Antagonists Based on Molecule Docking

P2Y12受体是存在于血小板表面的一种G蛋白偶联受体,在血小板聚集过程中发挥重要作用。其受体拮抗剂是一类抑制血小板聚集的药物,临床上主要用于预防和治疗由血小板异常聚集所致血栓性心脑血管疾病。氯吡格雷即为一种P2Y12受体拮抗剂,是目前临床上首选的抗血小板聚集药物之一,但因存在"氯吡格雷抵抗"等缺陷,其疗效受到极大影响。因此,新型P2Y12受体拮抗剂类抗血小板聚集药物的研发备受关注。综述应用分子对接技术进行的血小板P2Y12受体及其拮抗剂研究的最新进展,包括P2Y12受体与配体的结合模式以及P2Y12受体拮抗剂的构效关系研究,为高效低毒的抗血小板聚集新药的开发提供参考。

P2Y12 receptor found on the platelet surface as G-protein coupled receptor plays an important role in platelet aggregation. Its antagonists can inhibit platelet aggregation, which have been used mainly for the prevention and treatment of thrombotic cardio-cerebro vascular diseases induced by abnormal platelet aggregation in the clinic. Clopidogrel, a P2Y12 receptor antagonist, is one of clinically preferred anti-platelet aggregation drugs. But there has been ＂clopidogrel resistance＂ which affects its efficacy in the clinic. Therefore the development of novel P2Y12 receptor antagonists as anti-platelet aggregation drugs has attracted much attention. The current researches of platelet P2Y12 receptor and its antagonists based on molecule docking, including P2Y12 receptor-ligand binding modes and structure-activity relationship of P2Y12 receptor antagonists, were reviewed to provide a reference for the development of new anti- platelet aggregation drugs with high efficiency and low toxicity.