ArticleJournal of the American Chemical Society2025
Molecular Design of Unimolecular Tetra-Receptor Agonists.
Article in Journal of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Structural Dynamics of GLP-1 Analogues: Folding Energetics, Lipidation-Driven Assembly, and Aggregation Mechanisms.Molecules (Basel, Switzerland) · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Peptide hormone-receptor interactions serve as critical regulators of metabolic homeostasis, a paradigm exemplified by the clinical efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists. Building upon this framework, strategic design has yielded unimolecular dual and triple agonists targeting GLP-1R, glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon receptor (GcgR), leveraging the sequence homology within the cognate native ligands of the class B G protein-coupled receptor (GPCR) family. However, the integration of Y2 receptor (Y2R) agonism─engaged by peptide YY (PYY) and belonging to the structurally divergent class A GPCR family─has remained an unaddressed challenge due to the topological and sequence disparities between these receptor classes. Y2R activation plays a pivotal role in appetite suppression, potentiating the metabolic benefits conferred by GLP-1R, GIPR, and GcgR agonism. Here, we report first-in-class, unprecedented tetra-agonists with high potency at GLP-1R, GIPR, GcgR, and Y2R. The chimeric peptides overcome the intrinsic sequence constraints imposed by class A and class B GPCR divergence, demonstrating the feasibility of rationally designed agonism mediated by single agents across receptor families. Lipidation of this template is well tolerated enhancing the promise of therapeutic viability. Furthermore, we show that biased agonism at GLP-1R selectively boosts cyclic AMP (cAMP) signaling while minimizing β-arrestin recruitment, thereby decoupling receptor desensitization from metabolic efficacy. Additionally, we introduce a tunable framework to modulate β-arrestin engagement without compromising cAMP potency, providing insight into the fine-tuning of GPCR-mediated signaling for next-generation peptide therapeutics.
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What Socratic 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 Socratic graph.