GPCR biased ligands as novel heart failure therapeutics

Jonathan D. Violin; David G. Soergel; Guido Boerrigter; John C. Burnett; Michael W. Lark

doi:10.1016/j.tcm.2013.01.002

GPCR biased ligands as novel heart failure therapeutics

Jonathan D. Violin, David G. Soergel, Guido Boerrigter, John C. Burnett, Michael W. Lark

Cardiovascular Medicine

Research output: Contribution to journal › Review article › peer-review

31 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	242-249
Number of pages	8
Journal	Trends in cardiovascular medicine
Volume	23
Issue number	7
DOIs	https://doi.org/10.1016/j.tcm.2013.01.002
State	Published - Oct 2013

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.tcm.2013.01.002

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abstract = "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.",

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AU - Soergel, David G.

AU - Boerrigter, Guido

AU - Burnett, John C.

AU - Lark, Michael W.

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AB - 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.

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GPCR biased ligands as novel heart failure therapeutics

Abstract

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