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抗炎药物研发:广谱还是特异性趋化因子受体拮抗剂?

Anti-inflammatory drug development: Broad or specific chemokine receptor antagonists?

作者信息

Russo Remo Castro, Garcia Cristiana Couto, Teixeira Mauro Martins

机构信息

Universidade Federal de Minas Gerais, Departamento de Bioquímica e Imunologia, Pampulha, Belo Horizonte, MG, Brazil.

出版信息

Curr Opin Drug Discov Devel. 2010 Jul;13(4):414-27.

Abstract

Chemokines and chemokine receptors form a complex and diverse system known to be relevant for leukocyte activation and trafficking. There has been significant interest in the development of anti-inflammatory drugs that antagonize the function of chemokines or their receptors. However, the translation of results from animal models to human disease has not been simple, and drug development in the field has failed in many instances, leading to the question of whether targeting several chemokines may be more useful than targeting a single chemokine or receptor. This question has no simple answer. The complexity of the chemokine system may result in functional redundancy, which is not absolute. However, this complexity is likely important for the physiology of the immune system. The success of future development of therapies targeting chemokines and their receptors requires a complete understanding of the diversity and complexity of the system in human chronic inflammatory diseases and infection.

摘要

趋化因子和趋化因子受体构成了一个复杂多样的系统,已知该系统与白细胞激活和运输相关。人们对开发拮抗趋化因子或其受体功能的抗炎药物有着浓厚兴趣。然而,将动物模型的结果转化为人类疾病的研究并非易事,该领域的药物开发在许多情况下都失败了,这引发了一个问题,即靶向多种趋化因子是否比靶向单一趋化因子或受体更有用。这个问题没有简单的答案。趋化因子系统的复杂性可能导致功能冗余,但并非绝对。然而,这种复杂性可能对免疫系统的生理学很重要。未来针对趋化因子及其受体的治疗方法开发取得成功,需要全面了解该系统在人类慢性炎症性疾病和感染中的多样性和复杂性。

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