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Article

A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.

Cell genomics - 12 Nov 2025

Lin Ann, Spees Kaitlyn, Valbuena Raeline, Wirbel Jakob, Natarajan Aravind, Enright Nora, Bhatt Ami S, Bassik Michael C

Abstract excerpt

Non-olfactory G-protein-coupled receptors (GPCRs) regulate vital physiological functions and are targets for ∼34% of US Food and Drug Administration (FDA)-approved drugs. While small-molecule-activated GPCRs are well studied, there is growing interest in peptide GPCRs, particularly the melanocortin-4 receptor (MC4R), a key regulator of energy balance and appetite. Activation of MC4R by β-melanocyte-stimulating...

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Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

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Identifiers

PMID: 40930102
DOI: 10.1016/j.xgen.2025.100988
PMCID: PMC12648107

Genes

MC4R

Variants

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

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A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.PMID 40930102Read ↗

High resolution deep mutational scanning of the melanocortin-4 receptor enables target characterization for drug discoverySemantic proximity Read ↗

Human MC4R variants affect endocytosis, trafficking and dimerization revealing multiple cellular mechanisms involved in weight regulation.Semantic proximity Read ↗

Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against ObesitySemantic proximity Read ↗

MC4R Variants Modulate α-MSH and Setmelanotide Induced Cellular Signaling at Multiple LevelsSemantic proximity Read ↗

Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding.Semantic proximity Read ↗

Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor.Semantic proximity Read ↗

Functional studies on twenty novel naturally occurring melanocortin-4 receptor mutations.Semantic proximity Read ↗

Pharmacologic analyses of four chicken melanocortin-4 receptor mutations.Semantic proximity Read ↗

Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R human melanocortin-4 polymorphic receptors (hMC4Rs).Semantic proximity Read ↗

The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options.Semantic proximity Read ↗

Differential Signaling Profiles of MC4R Mutations with Three Different Ligands.Semantic proximity Read ↗

Pharmacological chaperones increase the cell-surface expression of intracellularly retained mutants of the melanocortin 4 receptor with unique rescuing efficacy profiles.Semantic proximity Read ↗

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