ArticleACS omega2019
Structural Modeling and in Silico Screening of Potential Small-Molecule Allosteric Agonists of a Glucagon-like Peptide 1 Receptor.
Article in ACS omega, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Understanding Biased Signaling and Small-Molecule Binding for Treatment of Type 2 Diabetes Mellitus and Obesity at the Glucagon-Like Peptide-1 Receptor (GLP-1R) Based on Molecular Dynamics Simulations.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- A membrane-permeable small molecule biosensor accesses intractable cells and animals without genetic manipulation.bioRxiv : the preprint server for biology · 2026Article
- Novel Small Molecule GLP-1R Agonists Based on 1Molecules (Basel, Switzerland) · 2026Article
- GLP-1R agonists: recent advances, current gaps, and future challenges.Molecular diversity · 2026Review
- Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes fromFrontiers in bioinformatics · 2024Article
- Article
- Small molecule allosteric modulation of the adenosine AFrontiers in endocrinology · 2023Review
- Assessing the Effect of Incretin Hormones and Other Insulin Secretagogues on Pancreatic Beta-Cell Function: Review on Mathematical Modelling Approaches.Biomedicines · 2022Review
- 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
- Bayesian metamodeling of complex biological systems across varying representations.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Discovery of Novel Allosteric Modulators Targeting an Extra-Helical Binding Site of GLP-1R Using Structure- and Ligand-Based Virtual Screening.Biomolecules · 2021Article
- Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist S6 Stimulates Insulin Secretion From Rat Islets.Frontiers in pharmacology · 2021Article
- Novel fatty chain-modified GLP-1R G-protein biased agonist exerts prolonged anti-diabetic effects through targeting receptor binding sites.RSC advances · 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
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The glucagon-like peptide 1 receptor (GLP-1R) belongs to the pharmaceutically important class B family of G-protein-coupled receptors (GPCRs), and its incretin peptide ligand GLP-1 analogs are adopted drugs for the treatment of type 2 diabetes. Despite remarkable antidiabetic effects, GLP-1 peptide-based drugs are limited by the need of injection. On the other hand, developing nonpeptidic small-molecule drugs targeting GLP-1R remains elusive. Here, we first constructed a three-dimensional structure model of the transmembrane (TM) domain of human GLP-1R using homology modeling and conformational sampling techniques. Next, a potential allosteric binding site on the TM domain was predicted computationally. In silico screening of druglike compounds against this predicted allosteric site has identified nine compounds as potential GLP-1R agonists. The independent agonistic activity of two compounds was subsequently confirmed using a cAMP response element-based luciferase reporting system. One compound was also shown to stimulate insulin secretion through in vitro assay. In addition, this compound synergized with GLP-1 to activate human GLP-1R. These results demonstrated that allosteric regulation potentially exists in GLP-1R and can be exploited for developing small-molecule agonists. The success of this work will help pave the way for small-molecule drug discovery targeting other class B GPCRs through allosteric regulations.
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.