靶向溶血磷脂酸受体的小分子激动剂和拮抗剂的研究进展

Development of the small molecule agonists and antagonists targeted on LPA receptors

溶血磷脂酸(LPA)可以与多种亚型受体结合,参与诸多信号调节,产生多种病理生理反应,它与心肌肥厚、肿瘤细胞的侵袭、转移和血管生成、器官纤维化、骨关节炎、神经性疼痛、精神分裂症多种疾病相关。靶向LPA受体的激动剂和拮抗剂是目前药物化学的研究热点。本文主要介绍小分子LPA受体激动剂和拮抗剂的结构及构效关系等方面的研究进展。

Lysophosphatidic acid （LPA） and its receptors, LPA1 - LPA6, are integral parts of signaling pathways involved in cellular proliferation, migration and survival. These signaling pathways are of therapeutic interest for the treatment of multiple types of cancer and to reduce cancer metastasis and side effects. Validated therapeutic potential of key receptors, as well as recent structure-activity relationships yielding compounds are exciting recent advances in the field. This review summarizes evaluation of LPA agonists and antagonists.