CCR2拮抗剂研究进展

Advances in study on chemokine receptor 2 antagonists

细胞表面趋化因子受体2(CCR2)属于G蛋白偶联受体(GPCR)超家族成员,并且是单核细胞趋化蛋白1～4(MCP1～4)的受体。MCP 1～4是促炎症反应的化学诱导物,CCR2和MCP-1在人类侵蚀性疾病模型如动脉粥状硬化、多发性硬化症中均起显著作用。大量研究证明CCR2和MCP-1拮抗剂可以减少临床炎症模型的发病率,这些化学拮抗剂的结构多样,主要包括γ-氨基丁酰胺类、甘胺酰胺类、噻唑类、吲哚类、二取代双哌啶醇类、季铵盐类和不饱和杂环类等,它们表现出不同的药理活性。CCR2拮抗剂对各种与趋化因子相关的疾病具有较好的疗效,部分药物已经进入临床试验阶段,综述CCR2及其受体拮抗剂的研究进展。

CC Chemokine Receptor 2 （CCR2） is a member of the G protein-coupled receptor （GPCR） superfamily that serves as the receptor for monocyte chemoattractant proteins 1-4 （MCP- 1 to -4）, a group of pro-inflammatory chemotactic cytokines （chemokines）. Many researches proved that CCR2 and the MCP-1 antagonist compound reduced the clinical inflammation model disease incidence rate, MCP-1 and CCR2 play the remarkable role in the human corrosive disease model like artery gruel shape hardening and the multiple scierosis. Its chemistry antagonist compound with the structural diversity, including 4-aminobutanamide antagonists, glycinamide antagonists, thiazole antagonists, indole antagonists, disubstituted piperidine alcohols antagonists, quaternary ammonium salts antagonists, and unsaturated heterocyclic antagonists, has displayed the different medicine activeness. CCR2 antagonists have good effect on various chemokine-related diseases, and some drugs have entered clinical trials. In this paper, CCR2 receptor antagonists aere reviewed.