摘要
骨关节炎(OA)是一种年龄相关性退行性疾病,以慢性关节疼痛、炎症和关节软骨损伤为特征。目前,甾体类药物和非甾体类抗炎药(NSAIDS)、选择性环氧合酶-2 (COX-2)抑制剂是治疗OA的一线药物。然而,这些药物可能会导致一些心血管副作用。因此,开发新的治疗OA的药物已成为当务之急。基质金属蛋白酶-13 (Matrix metalloproteinase, MMP-13)是基质金属蛋白酶家族(Matrix metalloproteinases, MMPs)的重要成员,通过降解关节软骨和骨组织中的II型胶原而发挥重要作用。值得注意的是,MMP-13在OA患者中异常表达,而在正常成人中不表达。此外,广谱MMP抑制剂可能会导致一些疼痛和关节僵硬的副作用,在临床试验中称为肌肉骨骼综合征(MSS)。因此,开发选择性MMP-13抑制剂是治疗OA的一个潜在策略。本文综述了选择性MMP-13抑制剂的研究进展,包括锌结合和非锌结合选择性MMP-13抑制剂两个亚家族。
关键词: 骨关节炎,关节软骨,MMP-13,锌结合基,构效关系,选择性抑制剂。
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