@article{b95cb44375684c2ba8aeb9e1aa1b181b,
title = "Discovery of (S)-2-cyclopentyl-N-((1-isopropylpyrrolidin2-yl)-9-methyl-1-oxo-2,9-dihydro-1H-pyrrido[3,4-b]indole-4-carboxamide (VU0453379): a novel, CNS penetrant glucagon-like peptide 1 receptor (GLP-1R) positive allosteric modulator (PAM)",
abstract = "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. ",
keywords = "Allosteric Regulation/drug effects, Animals, Catalepsy/chemically induced, Central Nervous System Agents/therapeutic use, Drug Synergism, Exenatide, Glucagon-Like Peptide 1/pharmacology, Glucagon-Like Peptide-1 Receptor, Haloperidol, High-Throughput Screening Assays, Indoles/chemical synthesis, Insulin/metabolism, Insulin Secretion, Islets of Langerhans/drug effects, Male, Mice, Inbred C57BL, Microsomes, Liver/metabolism, Peptides/pharmacology, Pyrrolidines/chemical synthesis, Receptors, Glucagon/drug effects, Structure-Activity Relationship, Venoms/pharmacology",
author = "Morris, {Lindsey C} and Nance, {Kellie D} and Gentry, {Patrick R} and Days, {Emily L} and Weaver, {C David} and Niswender, {Colleen M} and Thompson, {Analisa D} and Jones, {Carrie K} and Locuson, {Chuck W} and Morrison, {Ryan D} and Daniels, {J Scott} and Niswender, {Kevin D} and Lindsley, {Craig W}",
year = "2014",
month = dec,
day = "11",
doi = "10.1021/jm501375c",
language = "English",
volume = "57",
pages = "10192--7",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",
}