GPR81 agonist 1 is a highly potent and selective G protein-coupled receptor 81 (GPR81) agonist with EC50 values of 58nM for human and 50nM for mouse GPR81[1]. GPR81, as a lactate receptor, plays an important role in immune regulation[2]. GPR81 agonist 1 can inhibit lipolysis in differentiated 3T3-L1 adipocytes[3]. GPR81 agonist 1 can improve insulin resistance and liver inflammation by inhibiting the NLRP3 inflammasome signaling pathway[4].
In vivo, intraperitoneal injection of GPR81 agonist 1 (10mg/kg) in a breast cancer (BRCA) model mouse significantly reduced PD-L1 expression in tumor tissue but did not reduce tumor volume[5].
References:
[1] Sakurai T, Davenport R, Stafford S, et al. Identification of a novel GPR81-selective agonist that suppresses lipolysis in mice without cutaneous flushing[J]. European journal of pharmacology, 2014, 727: 1-7.
[2] Brown T P, Bhattacharjee P, Ramachandran S, et al. The lactate receptor GPR81 promotes breast cancer growth via a paracrine mechanism involving antigen-presenting cells in the tumor microenvironment[J]. Oncogene, 2020, 39(16): 3292-3304.
[3] Feingold K R, Moser A, Shigenaga J K, et al. Inflammation inhibits GPR81 expression in adipose tissue[J]. Inflammation Research, 2011, 60(10): 991-995.
[4] Zhang Y, Lu Q H, Cao H F, et al. Effects of GPR81 agonist on insulin resistance in rats with nonalcoholic fatty liver disease[J]. Chinese Journal of Applied Physiology, 2021, 37(4): 354-358.
[5] Guo S, Zhou J, Lou P, et al. Potentiated effects of lactate receptor GPR81 on immune microenvironment in breast cancer[J]. Molecular Carcinogenesis, 2023, 62(9): 1369-1377.
GPR81 agonist 1是一种高效、高选择性的G蛋白偶联受体81（GPR81）激动剂，对人和小鼠GPR81的EC50值分别为58nM和50nM[1]。蛋白偶联受体（GPR81）作为乳酸受体，在免疫调节中具有重要作用[2]。GPR81 agonist 1能够抑制分化的3T3-L1脂肪细胞的脂解[3]。GPR81 agonist 1能够通过抑制NLRP3炎症小体信号通路，改善胰岛素抵抗和肝脏炎症[4]。
在体内，GPR81 agonist 1（10mg/kg）通过腹腔注射治疗乳腺癌（BRCA）模型小鼠，显著降低了肿瘤组织中PD-L1的表达，但是没有减小肿瘤体积[5]。