Pharmacological therapy for cystic fibrosis: From bench to bedside
Pharmacological therapy for cystic fibrosis: From bench to bedside
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DOI：
10.1016/s1569-1993(11)60018-0
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发表时间：
2011-06-01
影响因子：
5.2
通讯作者：
Zegarra-Moran, Olga
中科院分区：
文献类型：
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作者：
Becq, Frederic;Mall, Marcus A.;Zegarra-Moran, Olga
随着对囊性纤维化跨膜传导调节因子（CFTR）的分子行为、其在囊性纤维化（CF）中的生理作用和功能障碍的了解，现在正在开发针对CF的根本原因而不是疾病症状的治疗策略。在这里，我们审查进展的发展，合理的新疗法的CF。我们强调发现的小分子拯救细胞表面表达和CF突变体的缺陷通道门控，分别称为CFTR校正剂和CFTR增效剂。我们提请注意恢复上皮离子转运到CF上皮的替代方法，包括上皮Na+通道（ENaC）的抑制剂和Ca 2+激活的Cl-通道TMEM 16 A的激活剂。将实验室中鉴定的小分子转化为CF患者药物所需的专业知识取决于我们在国际层面协调药物开发的能力以及我们使用合适疾病模型提供相关生物信息的能力。(C)2011年欧洲囊性纤维化协会。Elsevier B. V.出版，保留所有权利。
With knowledge of the molecular behaviour of the cystic fibrosis transmembrane conductance regulator (CFTR), its physiological role and dysfunction in cystic fibrosis (CF), therapeutic strategies are now being developed that target the root cause of CF rather than disease symptoms. Here, we review progress towards the development of rational new therapies for CF. We highlight the discovery of small molecules that rescue the cell surface expression and defective channel gating of CF mutants, termed CFTR correctors and CFTR potentiators, respectively. We draw attention to alternative approaches to restore epithelial ion transport to CF epithelia, including inhibitors of the epithelial Na+ channel (ENaC) and activators of the Ca2+-activated Cl- channel TMEM16A. The expertise required to translate small molecules identified in the laboratory to drugs for CF patients depends on our ability to coordinate drug development at an international level and our ability to provide pertinent biological information using suitable disease models. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.