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p38 MAP 激酶抑制剂的探索历程:从实验室到治疗炎症性疾病的临床应用。

The journey of p38 MAP kinase inhibitors: From bench to bedside in treating inflammatory diseases.

机构信息

Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, China.

The Rogel Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, United States.

出版信息

Eur J Med Chem. 2024 Dec 15;280:116950. doi: 10.1016/j.ejmech.2024.116950. Epub 2024 Oct 11.

Abstract

The p38 mitogen-activated protein kinase (MAPK) pathway is pivotal in regulating inflammatory responses and has emerged as a key target for the development of small-molecule inhibitors aimed at treating inflammatory diseases. In arthritis, especially rheumatoid arthritis (RA), the p38 MAPK pathway contributes to chronic inflammation and joint destruction by promoting the production of pro-inflammatory cytokines. Preclinical studies have shown that small-molecule inhibitors targeting the p38 MAPK pathway hold significant promise, exhibiting the potential to reduce inflammation and preserve joint integrity. Targeting this pathway presents a novel therapeutic approach to mitigating inflammation. This review traces the evolution of p38 MAP kinase inhibitors from initial laboratory studies to clinical candidates, underscoring their potential to significantly alter the treatment approach for inflammatory diseases.

摘要

p38 丝裂原活化蛋白激酶 (MAPK) 通路在调节炎症反应中起着关键作用,已成为开发旨在治疗炎症性疾病的小分子抑制剂的关键靶点。在关节炎,尤其是类风湿关节炎 (RA) 中,p38 MAPK 通路通过促进促炎细胞因子的产生,导致慢性炎症和关节破坏。临床前研究表明,靶向 p38 MAPK 通路的小分子抑制剂具有很大的应用前景,有可能减轻炎症并保持关节完整性。靶向该通路为减轻炎症提供了一种新的治疗方法。本综述追溯了 p38 MAP 激酶抑制剂从最初的实验室研究到临床候选药物的发展历程,强调了它们有潜力显著改变炎症性疾病的治疗方法。

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