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脾酪氨酸激酶:类风湿关节炎治疗干预的新靶点。

Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis.

作者信息

Bajpai Malini, Chopra Puneet, Dastidar Sunanda G, Ray Abhijit

机构信息

Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India.

出版信息

Expert Opin Investig Drugs. 2008 May;17(5):641-59. doi: 10.1517/13543784.17.5.641.

Abstract

BACKGROUND

In the last few years, significant progress has been made in understanding the pathogenic mechanisms and in defining the role of relevant cells and molecules in the pathophysiology of rheumatoid arthritis (RA). Various therapies, both biological (anti-TNF, anti-interleukins [e.g., IL-1]) and small molecule inhibitors have been explored for the treatment of RA.

OBJECTIVE

To date, no single signaling pathway inhibitor as wide acting as the corticosteroids, is known. However, treatment with corticosteroids is also associated with allied side effects. Despite a lot of efforts in the category of small molecule inhibitors, no inhibitor is available to deal with RA at both fronts (inflammation and tissue damage), without causing immense side effects.

METHOD

This present review explores the role of spleen tyrosine kinase (Syk) in the pathogenesis of RA and also discusses how it may meet the present day therapeutic requirements for the treatment of RA. This review gives an in-depth discussion on the role of Syk signaling in RA, the possibilities of using Syk as a target and also discusses the possible side effects that could be associated with its inhibition.

CONCLUSION

We propose Syk inhibition as a potential therapeutic approach for the treatment of RA.

摘要

背景

在过去几年中,在理解类风湿关节炎(RA)的发病机制以及确定相关细胞和分子在其病理生理学中的作用方面取得了重大进展。已经探索了各种疗法,包括生物疗法(抗TNF、抗白细胞介素[如IL-1])和小分子抑制剂来治疗RA。

目的

迄今为止,尚无一种作用范围像皮质类固醇那样广泛的单一信号通路抑制剂。然而,使用皮质类固醇进行治疗也会带来相关副作用。尽管在小分子抑制剂类别中付出了很多努力,但尚无一种抑制剂能够在不引起巨大副作用的情况下同时应对RA的两个方面(炎症和组织损伤)。

方法

本综述探讨了脾酪氨酸激酶(Syk)在RA发病机制中的作用,并讨论了它如何满足当今RA治疗的需求。本综述深入讨论了Syk信号在RA中的作用、将Syk用作靶点的可能性以及与其抑制相关的可能副作用。

结论

我们提出抑制Syk作为治疗RA的一种潜在治疗方法。

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