Recent progress in the development of small-molecule glucagon receptor antagonists.
The endocrine hormone glucagon stimulates hepatic glucose output via its action at the glucagon receptor (GCGr) in the liver. In the diabetic state, dysregulation of glucagon secretion contributes to abnormally elevated hepatic glucose output. The inhibition of glucagon-induced hepatic glucose output via antagonism of the GCGr using small-molecule ligands is a promising mechanism for improving glycemic control in the diabetic state. Clinical data evaluating the therapeutic potential of small-molecule GCGr antagonists is currently emerging. Recently disclosed clinical data demonstrates the potential efficacy and possible therapeutic limitations of small-molecule GCGr antagonists. Recent pre-clinical work on the development of GCGr antagonists is also summarized.
Cardiovascular, Metabolic and Endocrine Diseases Chemistry, Pfizer Worldwide Research and Development, 610 Main St, Cambridge, MA 02139, United States.
Matthew F
MF
Sammons
Cardiovascular, Metabolic and Endocrine Diseases Chemistry, Pfizer Worldwide Research and Development, 610 Main St, Cambridge, MA 02139, United States.
Esther C Y
EC
Lee
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D018027:Receptors, Glucagon; D054852:Small Molecule Libraries
Glucagon; Glucagon receptor antagonist; Small molecule antagonists; Type-2 diabetes