ReviewJournal of cellular and molecular medicine2022
MC4R biased signalling and the conformational basis of biological function selections.
Review in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.Cell genomics · 2025Article
- Polygenic Risk Score Associated with Gestational Diabetes Mellitus in an AmericanIndian Population.Journal of personalized medicine · 2025Article
- Melanocortin 4 receptor mutation in obesity.World journal of experimental medicine · 2024Review
- Structure elucidation of a human melanocortin-4 receptor specific orthosteric nanobody agonist.Nature communications · 2024Article
- Control of goal-directed and inflexible actions by dorsal striatal melanocortin systems, in coordination with the central nucleus of the amygdala.Progress in neurobiology · 2024Article
- Neural Progenitor Cells and the Hypothalamus.Cells · 2023Review
- G protein-coupled receptors and obesity.Frontiers in endocrinology · 2023Review
- MC4R biased signalling and the conformational basis of biological function selections.Journal of cellular and molecular medicine · 2022Review
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MC4R, a GPCR, has long been a major target for obesity treatment. As the most well-studied melanocortin receptor subtype, the evolutionary knowledge pushes the drug development and structure-activity relationship (SAR) moving forward. The past decades have witnessed the evolution of scientists' view on GPCRs gradually from the control of a single canonical signalling pathway via a bilateral 'active-inactive' model to a multi-state alternative model where the ligands' binding affects the selection of the downstream signalling. This evolution brings the concept of biased signalling and the beginning of the next generation of peptide drug development, with the aim of turning from receptor subtype specificity to signalling pathway selectivity. The determination of the value structures of the MC4R revealed insights into the working mechanism of MC4R activation upon binding of agonists. However, new challenge has risen as we seek to unravel the mystery of MC4R signalling selection. Thus, more biased agonists and ligands with representative biological functions are needed to solve the rest of the puzzle.
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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.