Synthesis and biological evaluation of an orally active ghrelin agonist that stimulates food consumption and adiposity in rats.
2-(2-Amino-2-methyl-propionylamino)-5-phenyl-pentanoic acid [1-[1-(4-methoxy-phenyl)-1-methyl-2-oxo-2-pyrrolidin-1-yl-ethyl]-1H-imidazol-4-yl]-amide (LY444711, 6) is an orally active ghrelin agonist that binds with high affinity to and is a potent activator of the growth hormone secretagogue receptor 1a (GHS-R1a) receptor. In rat models of feeding behavior and pharmacology, 6 creates a positive energy balance and induces adiposity by stimulating food consumption and sparing fat utilization. As an orally active ghrelin agonist, 6 represents a new pharmacological tool to investigate the orexigenic role of ghrelin in regulating energy homeostasis.
Lugar
Charles W
CW
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Clay
Michael P
MP
Lindstrom
Terry D
TD
Woodson
Andrea L
AL
Smiley
David
D
Heiman
Mark L
ML
Dodge
Jeffrey A
JA
D000273:Adipose Tissue / Q000187:drug effects* / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D004353:Drug Evaluation, Preclinical; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin; D008297:Male; D036361:Peptide Hormones / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000502:physiology; D054440:Receptors, Ghrelin
D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin