Drug-induced liver injury (DILI) is a common disorder that involves both direct liver cell toxicity and immune activation. The bile acid receptor, G-protein-coupled bile acid receptor 1 (GPBAR1; Takeda G-protein-coupled receptor 5 [TGR5]), and cysteinyl leukotriene receptor (CYSLTR) 1 are G-protein-coupled receptors activated by bile acids and leukotrienes, exerting opposite effects on cell-to-cell adhesion, inflammation, and immune cell activation. To investigate whether GPBAR1 and CYSLTR1 mutually interact in the development of DILI, we developed an orally active small molecule, CHIN117, that functions as a GPBAR1 agonist and CYSLTR1 antagonist.

中文翻译：

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G蛋白偶联胆汁酸受体1和半胱氨酰白三烯受体1的组合靶向揭示了胆汁酸和白三烯在药物性肝损伤中的机制作用

药物性肝损伤（DILI）是一种常见疾病，涉及直接肝细胞毒性和免疫激活。胆汁酸受体、G蛋白偶联胆汁酸受体 1 (GPBAR1；武田 G 蛋白偶联受体 5 [TGR5]) 和半胱氨酰白三烯受体 (CYSLTR) 1 是由胆汁酸激活的 G 蛋白偶联受体，白三烯，对细胞间粘附、炎症和免疫细胞激活产生相反的作用。为了研究 GPBAR1 和 CYSLTR1 在 DILI 的发生过程中是否相互相互作用，我们开发了一种口服活性小分子 CHIN117，它充当 GPBAR1 激动剂和 CYSLTR1 拮抗剂。