Phosphodiesterase-4 as a therapeutic target

被引：521

作者：

Houslay, MD

Schafer, P

Zhang, KYJ

机构：

[1] Univ Glasgow, Div Biochem & Mol Biol, IBLS, Glasgow G12 8QQ, Lanark, Scotland

[2] Celgene, Drug Discovery Dept, Immunotherapeut Div, Summit, NJ 07901 USA

[3] Plexxikon, Dept Biol Struct, Berkeley, CA 94710 USA

来源：

DRUG DISCOVERY TODAY | 2005年 / 10卷 / 22期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/S1359-6446(05)03622-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Cyclic AMP (CAMP) is a key second messenger in all cells. It is compartmentalized within cells and its levels are controlled, as a result of spatially discrete signaling cassettes controlling its generation, detection and degradation. Underpinning compartmentalized CAMP signaling are similar to 20 members of the phosphodiesterase-4 (PDE4) family. The selective inhibition of this family generates profound, functional effects and PDE4 inhibitors are currently under development to provide potential, novel therapeutics for the treatment of inflammatory diseases, such as asthma, chronic obstructive pulmonary disease and psoriasis, as well as treating depression and serving as cognitive enhancers. Here, we delineate the range of PDE4 isoforms, their role in signaling, their structural biology and related preclinical and clinical pharmacology.

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页码：1503 / 1519

页数：17

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