Duksung Women's University, College of Pharmacy, Seoul, Korea.
Expert Opin Investig Drugs. 2009 Dec;18(12):1893-905. doi: 10.1517/13543780903321490.
The p38 mitogen-activated protein kinase (MAPK) is activated by various pro-inflammatory and stressful stimuli. Mounting evidence suggests that the p38 MAPK signaling cascade is involved in various biological responses other than inflammation such as cell proliferation, differentiation, apoptosis and invasion, suggesting that the p38 MAPK can serve as a potential therapeutic target for the treatment of not only inflammatory diseases but also cancer.
The unique characteristics of p38 MAPK are summarized with regard to activation and function of p38 MAPK signaling cascades. We then discuss the involvement of p38 MAPK in diseases and the implications of the possible therapeutic use of p38 MAPK inhibitors. The p38 MAPK inhibitors that have been used in the in vitro/in vivo systems as well as in the clinical trials are summarized.
RESULTS/CONCLUSION: The p38 MAPK plays an important role in key cellular processes related to inflammation and cancer. Understanding the signal transduction mechanisms and gene regulation by p38 MAPK provides useful information in the development of p38 MAPK inhibitors with therapeutic benefits with reduced side effects. In this review, we summarize and present the list of p38 MAPK inhibitors in in vitro/in vivo studies as well as in clinical trials.
p38 丝裂原活化蛋白激酶（MAPK）可被各种促炎和应激刺激激活。越来越多的证据表明，p38 MAPK 信号级联参与了除炎症以外的各种生物学反应，如细胞增殖、分化、凋亡和侵袭，这表明 p38 MAPK 可以作为一种潜在的治疗靶点，不仅可用于治疗炎症性疾病，还可用于治疗癌症。
总结了 p38 MAPK 的独特特征，包括 p38 MAPK 信号级联的激活和功能。然后，我们讨论了 p38 MAPK 在疾病中的作用以及使用 p38 MAPK 抑制剂的可能治疗意义。总结了已在体外/体内系统以及临床试验中使用的 p38 MAPK 抑制剂。
结果/结论：p38 MAPK 在与炎症和癌症相关的关键细胞过程中发挥重要作用。了解 p38 MAPK 的信号转导机制和基因调控为开发具有治疗益处且副作用较小的 p38 MAPK 抑制剂提供了有用信息。在这篇综述中，我们总结并列出了在体外/体内研究以及临床试验中使用的 p38 MAPK 抑制剂。
