Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, 65962 Frankfurt, Germany.
Bioorg Med Chem Lett. 2012 Aug 15;22(16):5239-43. doi: 10.1016/j.bmcl.2012.06.057. Epub 2012 Jun 27.
Lysophosphatidic acid (LPA) is a potent activator of human platelets in vitro. Recently, the G protein-coupled receptor LPA5/GPR92 has been identified to be the relevant LPA receptor responsible for the activation of human platelets by LPA. In a high-throughput screening campaign we identified a diphenyl pyrazole carboxylic acid as a small-molecule inhibitor for LPA5. Confirmation for the specificity of this small molecule was achieved in human platelets as the relevant cellular in vitro model. We could confirm using antagonists for alternative LPA receptors that we identified in our work the first non-lipid, small-molecule inhibitor for LPA5/GPR92 specifically inhibiting LPA-mediated platelet activation in vitro.
溶血磷脂酸（LPA）是体外人血小板的有效激活剂。最近，G 蛋白偶联受体 LPA5/GPR92 已被确定为与 LPA 激活人血小板相关的受体。在高通量筛选活动中，我们发现二苯吡唑羧酸是 LPA5 的小分子抑制剂。在作为相关细胞体外模型的人血小板中，证实了这种小分子的特异性。我们可以使用替代 LPA 受体的拮抗剂来证实，我们在工作中首次发现了非脂类、小分子 LPA5/GPR92 抑制剂，特异性抑制体外 LPA 介导的血小板激活。
