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)
Research output: Contribution to journal › Journal article › Research › peer-review
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.
| Original language | English |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| Volume | 57 |
| Issue number | 23 |
| Pages (from-to) | 10192-7 |
| Number of pages | 6 |
| ISSN | 0022-2623 |
| DOIs | |
| Publication status | Published - 11 Dec 2014 |
| Externally published | Yes |
- 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
Research areas
ID: 213599458