Body weight regulation by selective MC4 receptor agonists and antagonists.
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.
Foster
Alam C
AC
Neurocrine Biosciences Inc, San Diego, California 92121, USA. afoster@neurocrine.com
Joppa
Margaret
M
Markison
Stacy
S
Gogas
Kathy R
KR
Fleck
Beth A
BA
Murphy
Brian J
BJ
Wolff
Meira
M
Cismowski
Mary J
MJ
Ling
Nicholas
N
Goodfellow
Val S
VS
Chen
Chen
C
Saunders
John
J
Conlon
Paul J
PJ
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
D008024:Ligands; D010455:Peptides; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH