Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 57, Issue 23, Pages 10192-10197Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm501375c
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Funding
- Tennessee Valley Healthcare System
- NIH [GM06232]
- Warren Family
- Foundation for establishing the William K. Warren, Jr. Chair in Medicine
- Culpepper Medical Scholarship
- American Diabetes Association
- Vanderbilt Diabetes and Research Training Center
- Vanderbilt Diabetes and Research Training Center [DK020593]
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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.
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