title: Regulation of the Apelinergic System and Its Potential in Cardiovascular Disease: Peptides and Small Molecules as Tools for Discovery.
abstract: Apelin peptides and the apelin receptor represent a relatively new therapeutic axis for the potential treatment of cardiovascular disease. Several reports suggest apelin receptor activation with apelin peptides results in cardioprotection as noted through positive ionotropy, angiogenesis, reduction of mean arterial blood pressure, and apoptosis. Considering the potential therapeutic benefit attainable through modulation of the apelinergic system, research is expanding to develop novel therapies that limit the inherent rapid degradation of endogenous apelin peptides and produce metabolically stable small molecule agonists and antagonists to more rigorously interrogate the apelin receptor system. This review details the structure-activity relationships for chemically modified apelin peptides and recent disclosures of small molecule agonists and antagonists and summarizes the peer reviewed and patented literature. Development of metabolically stable ligands of apelin receptor and their effects in various models over the coming years will hopefully lead to establishment of this receptor as a validated target for cardiovascular indications.
authors.affiliation: Center for Drug Discovery, Research Triangle Institute , Post Office Box 12194, Research Triangle Park, North Carolina 27709-2194, United States.
authors.forename: Sanju
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Center for Drug Discovery, Research Triangle Institute , Post Office Box 12194, Research Triangle Park, North Carolina 27709-2194, United States.
authors.forename: Danni L
authors.initials: DL
authors.lastname: Harris
authors.affiliation: Center for Drug Discovery, Research Triangle Institute , Post Office Box 12194, Research Triangle Park, North Carolina 27709-2194, United States.
authors.forename: Rangan
authors.initials: R
authors.lastname: Maitra
authors.affiliation: Center for Drug Discovery, Research Triangle Institute , Post Office Box 12194, Research Triangle Park, North Carolina 27709-2194, United States.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Runyon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics; D054852:Small Molecule Libraries
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D054852:Small Molecule Libraries