Recent progress in the development of small-molecule glucagon receptor antagonists

Matthew F Sammons; Esther C Y Lee

doi:10.1016/j.bmcl.2015.07.092

Recent progress in the development of small-molecule glucagon receptor antagonists

Bioorg Med Chem Lett. 2015 Oct 1;25(19):4057-64. doi: 10.1016/j.bmcl.2015.07.092. Epub 2015 Aug 1.

Authors

Matthew F Sammons¹, Esther C Y Lee¹

Affiliation

¹ Cardiovascular, Metabolic and Endocrine Diseases Chemistry, Pfizer Worldwide Research and Development, 610 Main St, Cambridge, MA 02139, United States.

PMID: 26271588
DOI: 10.1016/j.bmcl.2015.07.092

Abstract

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.

Keywords: Glucagon; Glucagon receptor antagonist; Small molecule antagonists; Type-2 diabetes.

Publication types

Review

MeSH terms

Animals
Dose-Response Relationship, Drug
Humans
Molecular Structure
Receptors, Glucagon / antagonists & inhibitors*
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship

Substances

Receptors, Glucagon
Small Molecule Libraries