蛋白激酶C、JAK、磷酸二脂酶的小分子抑制剂在银屑病治疗中的研究进展

Small-molecule inhibitors of protein kinase C, the Janus kinases （JAK） pathway and phosphodiesterases in the treatment of psoriasis

银屑病是一种慢性复发性炎症性疾病，临床表现为皮肤的鳞屑性红斑，部分患者可累及关节。尽管目前针对特异性炎症性细胞因子和免疫细胞的生物制剂在银屑病治疗中取得了较为满意的疗效，但仍缺乏长期安全有效而经济的治疗药物。小分子抑制剂是一些相对分子质量〈1000的化合物，主要针对一些细胞内信号通路或分子靶点，如蛋白激酶C、JAK通路、磷酸二酯酶等。小分子抑制剂最初在一些自身免疫性疾病和炎症性疾病中应用，现已进入寻常性银屑病和关节病性银屑病的Ⅱ期和Ⅲ期临床试验并取得了较为满意的疗效。因此，小分子抑制剂有望成为治疗银屑病的选择之一。

Psoriasisis a chronic recurrent inflammatory skin disorder clinically characterized by scaly erythema with occasional involvement of joints. Although biological therapies targeting specific inflammatory pathways have proved to be highly effective in recent years, there are no economical drugs for psoriasis with long-term effectiveness. Small-molecule inhibitors （SMIs）, a group of compounds with relative molecular weights less than 1 000, mainly target intracellular signaling pathways or molecules, such as protein kinase C, the Janus kinases （JAK） pathway and phosphodiesterases. They were previously developed to treat some autoimmune disorders and inflammatory diseases, and have shown favorable efficacy for the treatment of psoriasis vulgaris and psoriatic arthritis in phase Ⅱ and Ⅲ clinical trials. Hence, SMIs are expected to become a novel option for the management of psoriasis in the future.