Advances in targeting cyclic nucleotide phosphodiesterases.
Advances in targeting cyclic nucleotide phosphodiesterases.
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DOI：
10.1038/nrd4228
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发表时间：
2014-04
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影响因子：
--
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中科院分区：
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--
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环核苷酸磷酸二酯酶（PDEs）催化环AMP和环GMP的水解，从而调节这些环核苷酸的细胞内浓度、它们的信号通路，从而调节健康和疾病中的无数生物反应。目前，少量PDE抑制剂在临床上用于治疗几种疾病中环核苷酸信号的病理生理失调，包括勃起功能障碍、肺动脉高压、急性难治性心力衰竭、间歇性跛行和慢性阻塞性肺疾病。然而，由于对个体PDE在调节特定环核苷酸信号通路的亚细胞区隔化中的作用的理解日益加深，新型特异性抑制剂的基于结构的设计以及针对个体PDE变体的更复杂策略的发展，PDE的制药兴趣已被重新点燃。
Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.
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影响因子：
4.1
作者：
Ahmad, Faiyaz;Lindh, Rebecka;Manganiello, Vincent C.
通讯作者：
Manganiello, Vincent C.
影响因子：
3.5
作者：
Beard, MB;O'Connell, JC;Houslay, MD
通讯作者：
Houslay, MD
影响因子：
3.6
作者：
Bajpai, M;Fiedler, SE;Carr, DW
通讯作者：
Carr, DW
影响因子：
2.9
作者：
Black, Keith L.;Yin, Dali;Ong, John M.;Hu, Jinwei;Konda, Bindu M.;Wang, Xiao;Ko, MinHee K.;Bayan, Jennifer-Ann;Sacapano, Manuel R.;Espinoza, Andreas;Irvin, Dwain K.;Shu, Yan
通讯作者：
Shu, Yan
影响因子：
2.7
作者：
Banerjee, Abhisek;Patil, Sandip;Gharat, Laxmikant A.
通讯作者：
Gharat, Laxmikant A.