GPCR biased ligands as novel heart failure therapeutics

被引：29
作者：
Violin, Jonathan D. [1 ]
Soergel, David G. [1 ]
Boerrigter, Guido [2 ]
Burnett, John C., Jr. [2 ]
Lark, Michael W. [1 ]
机构：
[1] Treuena Inc, King Of Prussia, PA 19406 USA
[2] Mayo Clin & Mayo Fdn, Cardiorenal Res Lab, Rochester, MN 55905 USA
来源：
TRENDS IN CARDIOVASCULAR MEDICINE | 2013年 / 23卷 / 07期
关键词：
ANGIOTENSIN-II RECEPTOR; WORSENING RENAL-FUNCTION; BETA-ARRESTIN; CLINICAL-TRIALS; PATHWAYS; 1A; ACTIVATION; HYPERTENSION; MANAGEMENT; THERAPY;
D O I：
10.1016/j.tcm.2013.01.002
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
G protein-coupled receptors have been successfully targeted by numerous therapeutics including drugs that have transformed the management of cardiovascular disease. However, many GPCRs, when activated or blocked by drugs, elicit both beneficial and adverse pharmacology. Recent work has demonstrated that in some cases, the salutary and deleterious signals linked to a specific GPCR can be selectively targeted by "biased ligands" that entrain subsets of a receptor's normal pharmacology. This review briefly summarizes the advances and current state of the biased ligand field, focusing on an example: biased ligands targeting the angiotensin II type 1 receptor. These compounds exhibit unique pharmacology, distinct from classic agonists or antagonists, and one such molecule is now in clinical development for the treatment of acute heart failure. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码：242 / 249
页数：8
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