Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities

被引:37
作者
Bhave, Gautam [1 ,3 ]
Lonergan, Daniel [1 ]
Chauder, Brian A. [2 ]
Denton, Jerod S. [1 ,2 ,4 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Digest Dis Res Ctr, Nashville, TN 37232 USA
关键词
RECTIFYING POTASSIUM CHANNELS; CELLULAR CONDUCTIVE PATHWAYS; ANTENATAL BARTTER-SYNDROME; CORTICAL COLLECTING DUCT; THICK ASCENDING LIMBS; SUBUNIT KNOCKOUT MICE; BASOLATERAL MEMBRANE; ATRIAL-FIBRILLATION; CRYSTAL-STRUCTURE; GIRK CHANNELS;
D O I
10.4155/FMC.10.179
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Inward rectifier potassium (Kir) channels have been postulated as therapeutic targets for several common disorders including hypertension, cardiac arrhythmias and pain. With few exceptions, however, the small-molecule pharmacology of this family is limited to nonselective cardiovascular and neurologic drugs with off-target activity toward inward rectifiers. Consequently, the actual therapeutic potential and 'drugability' of most Kir channels has not yet been determined experimentally. The purpose of this review is to provide a comprehensive summary of publicly disclosed Kir channel small-molecule modulators and highlight recent targeted drug-discovery efforts toward Kir1.1 and Kir2.1. The review concludes with a brief speculation on how the field of Kir channel pharmacology will develop over the coming years and a discussion of the increasingly important role academic laboratories will play in this progress.
引用
收藏
页码:757 / 774
页数:18
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