ArticleProceedings of the National Academy of Sciences of the United States of America2007
A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 167 citations in OpenAlex.
- Effect of liraglutide on expression of inflammatory genes in type 2 diabetes.Scientific reports · 2021Trial
- From Phytochemistry to Metabolic Regulation: The Insulin-Promoting Effects of Loureirin B Analogous to an Agonist of GLP-1 Receptor.International journal of molecular sciences · 2025Article
- Small-Molecule GLP-1 Receptor Agonists: A Promising Pharmacological Approach.Medicina (Kaunas, Lithuania) · 2025Review
- Article
- Synthesis of Bis(amino acids) Containing the Styryl-cyclobutane Core by Photosensitized [2+2]-Cross-cycloaddition of Allylidene-5(4International journal of molecular sciences · 2023Article
- GLP-1R Signaling and Functional Molecules in Incretin Therapy.Molecules (Basel, Switzerland) · 2023Review
- A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor.Journal of medicinal chemistry · 2022Article
- 2-Aminothiophene derivatives as a new class of positive allosteric modulators of glucagon-like peptide 1 receptor.Chemical biology & drug design · 2022Article
- Structural basis of peptidomimetic agonism revealed by small- molecule GLP-1R agonists Boc5 and WB4-24.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Stereoselective, Ruthenium-Photocatalyzed Synthesis of 1,2-Diaminotruxinic Bis-amino Acids from 4-Arylidene-5(4The Journal of organic chemistry · 2022Article
- Non-peptide agonists and positive allosteric modulators of glucagon-like peptide-1 receptors: Alternative approaches for treatment of Type 2 diabetes.British journal of pharmacology · 2022Review
- Reactivity of (The Journal of organic chemistry · 2021Article
- Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening.Biomolecules · 2021Article
- Ligand-Receptor Interactions and Machine Learning in GCGR and GLP-1R Drug Discovery.International journal of molecular sciences · 2021Article
- Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural Basis for Allosteric Modulation of Class B G Protein-Coupled Receptors.Annual review of pharmacology and toxicology · 2020Review
- Article
- Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore.Beilstein journal of organic chemistry · 2020Article
- Discovery of a potential positive allosteric modulator of glucagon-like peptide 1 receptor through virtual screening and experimental study.Journal of computer-aided molecular design · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peptidic mimics of the gut hormone glucagon-like peptide (GLP) 1, exemplified by the recently approved drug exenatide, show promise as therapies for type 2 diabetes. Such "incretin mimetics" regulate glucose appearance in the plasma and can restore glucose-stimulated insulin secretion without excess risk of hypoglycemia. The need for injection, which may limit the use of peptidic GLP-1 receptor (GLP-1R) agonists, has driven largely unsuccessful efforts to find smaller molecules. The failure to identify orally effective agonists has instead promoted the indirect approach of inhibiting the GLP-1-degrading enzyme dipeptidyl peptidase IV. Here we report a nonpeptidic GLP-1R agonist with sufficient activity to evoke effects in whole animals, including antidiabetic efficacy in db/db mice. Two substituted cyclobutanes (S4P and Boc5) were developed after screening a compound library against a cell line stably cotransfected with GLP-1R and a cAMP-responsive reporter. Each bound to GLP-1R and increased intracellular cAMP. Agonist effects were blocked by the GLP-1R antagonist exendin(9-39). Boc5 amplified glucose-stimulated insulin secretion in isolated rat islets. Both i.p. and oral administration of Boc5 dose-dependently inhibited food intake in mice, an effect that could be blocked by pretreatment with exendin(9-39). Daily injections of Boc5 into db/db mice reduced HbA1c to nondiabetic values, an effect not observed in ad libitum-fed or pair-fed diabetic controls. Thus, Boc5 behaved as a full GLP-1 mimetic in vitro and in vivo. The chemical genus represented by Boc5 may prompt the exploration of orally available GLP-1R agonists with potential utility in diabetes and obesity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.