Morris LC, Nance KD, Gentry PR, Days EL, Weaver CD, Niswender CM, Thompson AD, Jones CK, Locuson CW, Morrison RD, Daniels JS, Niswender KD, Lindsley CW
J Med Chem. 2014 57 (23)
· PMCID: PMC4266362
A duplexed, functional multiaddition high throughput screen and subsequent iterative parallel synthesis effort identified the first highly selective and CNS penetrant glucagon-like peptide-1R (GLP-1R) positive allosteric modulator (PAM). PAM (S)-9b potentiated low-dose exenatide to augment insulin secretion in primary mouse pancreatic islets, and (S)-9b alone was effective in potentiating endogenous GLP-1R to reverse haloperidol-induced catalepsy.
MeSH Terms (22)Allosteric Regulation Animals Catalepsy Central Nervous System Agents Drug Synergism Exenatide Glucagon-Like Peptide-1 Receptor Glucagon-Like Peptide 1 Haloperidol High-Throughput Screening Assays Indoles Insulin Insulin Secretion Islets of Langerhans Male Mice, Inbred C57BL Microsomes, Liver Peptides Pyrrolidines Receptors, Glucagon Structure-Activity Relationship Venoms