title: Body weight regulation by selective MC4 receptor agonists and antagonists.
abstract: There has been great interest in melanocortin (MC) receptors as targets for the design of novel therapeutics to treat disorders of body weight, such as obesity and cachexia. Both genetic and pharmacological evidence points toward central MC4 receptors as the principal target. Using highly selective peptide tools for the MC4 receptor, which have become available recently, we have provided pharmacological confirmation that central MC4 receptors are the prime mediators of the anorexic and orexigenic effects reported for melanocortin agonists and antagonists, respectively. The current progress with receptor-selective small molecule agonist and antagonist drugs should enable the therapeutic potential of MC4 receptor activation and inhibition to be assessed in the clinic in the near future.
authors.affiliation: Neurocrine Biosciences Inc, San Diego, California 92121, USA. afoster@neurocrine.com
authors.forename: Alam C
authors.initials: AC
authors.lastname: Foster
authors.forename: Margaret
authors.initials: M
authors.lastname: Joppa
authors.forename: Stacy
authors.initials: S
authors.lastname: Markison
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Gogas
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fleck
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Murphy
authors.forename: Meira
authors.initials: M
authors.lastname: Wolff
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Cismowski
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ling
authors.forename: Val S
authors.initials: VS
authors.lastname: Goodfellow
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Conlon
mesh_terms: D000818:Animals; D000855:Anorexia / Q000378:metabolism; D001835:Body Weight; D004435:Eating; D006706:Homeostasis; D006801:Humans; D008024:Ligands; D009765:Obesity / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000521:alpha-MSH / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D010455:Peptides; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH