在过去的十年里,对鞘氨醇-1-磷酸受体2(S1PR2)的研究显着增加,是一种G蛋白偶联受体.在被S1P或其他配体激活后,S1PR2启动下游信号通路,如磷酸肌醇3-激酶(PI3K),丝裂原活化蛋白激酶(MAPK),Rho/Rho相关的含卷曲螺旋激酶(ROCK),和其他人,有助于S1PR2的多种生物学功能,并在各种生理过程和疾病进展中发挥关键作用,比如多发性硬化症,纤维化,炎症,和肿瘤。由于S1PR2广泛的生物学功能,许多S1PR2调节剂,包括激动剂和拮抗剂,已由制药公司开发和发现(例如,诺华和加拉帕戈斯NV)以及用于疾病诊断和治疗的学术药物化学家。然而,很少发表全面概述S1PR2功能和监管机构的评论。在这里,我们对S1PR2及其调制器的功能进展进行了深入回顾。我们起首综述了S1PR2的构造、生物学功效及其在人类疾病中的病理感化。然后我们专注于发现方法,设计策略,发展过程,和S1PR2调节剂的生物医学应用。此外,我们概述了这一领域的主要挑战和未来方向。我们的全面审查将有助于发现和开发更有效和临床适用的S1PR2调节剂。
Over the past decade, there has been a notable increase in research on sphingosine-1-phosphate receptor 2 (S1PR2), which is a type of G-protein-coupled receptor. Upon activation by S1P or other ligands, S1PR2 initiates downstream signaling pathways such as phosphoinositide 3-kinase (PI3K), Mitogen-activated protein kinase (MAPK), Rho/Rho-associated coiled-coil containing kinases (ROCK), and others, contributing to the diverse biological functions of S1PR2 and playing a pivotal role in various physiological processes and disease progressions, such as multiple sclerosis, fibrosis, inflammation, and tumors. Due to the extensive biological functions of S1PR2, many S1PR2 modulators, including
agonists and antagonists, have been developed and discovered by pharmaceutical companies (e.g., Novartis and Galapagos NV) and academic medicinal chemists for disease diagnosis and treatment. However, few reviews have been published that comprehensively overview the functions and regulators of S1PR2. Herein, we provide an in-depth review of the advances in the function of S1PR2 and its modulators. We first summarize the structure and biological function of S1PR2 and its pathological role in human diseases. We then focus on the discovery approach, design strategy, development process, and biomedical application of S1PR2 modulators. Additionally, we outline the major challenges and future directions in this field. Our comprehensive review will aid in the discovery and development of more effective and clinically applicable S1PR2 modulators.