Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 60, Issue 4, Pages 1611-1616Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01706
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Funding
- NIH [GM06232]
- Warren Family and Foundation
- American Diabetes Association research award
- Vanderbilt Diabetes and Research Training Center Pilot and Feasibility award
- Vanderbilt Diabetes and Research Training Center [DK020593]
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A duplexed, functional multiaddition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon like peptide-1 receptor (GLP-1R) noncompetitive antagonist. Antagonist 5d not only blocked exendin-4-stimulated insulin release in islets but also lowered insulin levels while increasing blood glucose in vivo.
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