GLPwatch
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).
J Med Chem · 2014
Last updated 2026-05-28Researchers discovered a new compound, (S)-9b, that enhances the effects of GLP-1 drugs like exenatide. In lab tests, (S)-9b boosted insulin production in mouse pancreatic cells and improved movement issues caused by a drug called haloperidol.
AI summary of the abstract below.
| Journal | J Med Chem, 2014 |
|---|---|
| Citations | 37 |
| Relative citation ratio | 1.27 |
| NIH percentile | 59 |
| Molecules | — |
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.
Verbatim abstract via PubMed 25423411 ↗