Nance KD, Days EL, Weaver CD, Coldren A, Farmer TD, Cho HP, Niswender CM, Blobaum AL, Niswender KD, Lindsley CW
J Med Chem. 2017 60 (4)
A duplexed, functional multiaddition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) noncompetitive antagonist. Antagonist 5d not only blocked exendin-4-stimulated insulin release in islets but also lowered insulin levels while increasing blood glucose in vivo.
MeSH Terms (13)Administration, Oral Animals Blood Glucose Cells, Cultured Central Nervous System Glucagon-Like Peptide-1 Receptor Halogenation Humans Insulin Islets of Langerhans Male Pyrimidines Rats, Sprague-Dawley