title: GPCR biased ligands as novel heart failure therapeutics.
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.
authors.affiliation: Trevena Inc, 1018 West 8th Ave, Suite A, King of Prussia, PA 19406. Electronic address: jviolin@trevenainc.com.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Violin
authors.forename: David G
authors.initials: DG
authors.lastname: Soergel
authors.forename: Guido
authors.initials: G
authors.lastname: Boerrigter
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Michael W
authors.initials: MW
authors.lastname: Lark
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism / Q000494:pharmacology; D055808:Drug Discovery; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods; D043562:Receptors, G-Protein-Coupled / Q000145:classification / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D008024:Ligands; D043562:Receptors, G-Protein-Coupled