Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China.
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Drug Discov Today. 2018 Jun;23(6):1187-1202. doi: 10.1016/j.drudis.2018.01.015. Epub 2018 Jan 9.
Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4 (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A domain of LPS, leading to the activation of downstream signaling of cytokine and chemokine production, and initiation of inflammatory and immune responses. However, excessive activation and potent host responses generate severe inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly being considered as an attractive pharmacological target for the development of potent anti-inflammatory agents. In this Keynote review, we provide a comprehensive overview of the recent advances in the structure and biology of MD2, and present MD2 modulators as promising agents for anti-inflammatory intervention.
髓样分化蛋白 2（MD2）与 Toll 样受体 4（TLR4）结合，高亲和力地结合脂多糖（LPS），诱导形成激活的同源二聚体 LPS-MD2-TLR4。MD2 直接识别 LPS 的脂质 A 结构域，导致细胞因子和趋化因子产生的下游信号通路激活，并引发炎症和免疫反应。然而，过度的激活和强烈的宿主反应会产生严重的炎症综合征，如急性败血症和败血症性休克。MD2 正日益被认为是开发强效抗炎药物的有吸引力的药理学靶点。在这个主题综述中，我们全面概述了 MD2 的结构和生物学方面的最新进展，并提出了 MD2 调节剂作为抗炎干预的有前途的药物。
