p38丝裂原活化蛋白激酶抑制剂研究进展

p38丝裂原活化蛋白激酶（MAPK）通路是细胞内应激反应信号通路,与炎症反应密切相关。炎症反应失控是很多疾病产生的重要原因之一,传统抗炎药物的严重副作用使得寻找强效、安全的抗炎药物极为迫切。通过抑制剂调节信号通路的炎症药物研发成为目前发展的趋势,而p38MAPK的中心地位使其成为首选靶点。p38MAPK抑制剂和p38MAPK的研究进展相辅相成,发展迅速。已报道的100多种不同化学结构的p38MAPK特异性抑制剂中已有20多种进入临床试验阶段,但至今尚没有一种化合物被批准应用于临床治疗。我们讨论了p38MAPK抑制剂的研究现状和研究策略。

Recent Advance on p38 Mitogen-Activated Protein Kinases Inhibitors

As a stress-activated signaling pathway, p38 mitogen-activated protein kinases（MAPK） pathway plays a very important role in inflammation. Uncontrolled inflammation is involved in many diseases. Thus, relatively non-selective and dose-limiting side-effects of traditional drugs highlighting the need of potent, safe, effective anti-inflammatory drugs. Regulating signaling pathways with specific inhibitors to balance inflammation has been the trend, p38 MAPK was chosen as the therapeutic target for its central role in the production of inflammatory molecules. More than one hundred p38 MAPK inhibitors with diverse chemical structures have been reported, however, only about twenty have entered clinical trails, and no one has been approved so far. Novel strategies for inhibition of p38 MAPK pathway have been discussed here.