The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options
Abstract
Obesity is one of the greatest public health challenges of the 21st century. Obesity is currently responsible for ∼0.7-2.8% of a country's health costs worldwide. Treatment is often not effective because weight regulation is complex. Appetite and energy control are regulated in the brain. Melanocortin-4 receptor (MC4R) has a central role in this regulation. MC4R defects lead to a severe clinical phenotype with lack of satiety and early-onset severe obesity. Preclinical research has been carried out to understand the mechanism of MC4R regulation and possible effectors. The objective of this study is to systematically review the literature for emerging pharmacological obesity treatment options. A systematic literature search was performed in PubMed and Embase for articles published until June 2012. The search resulted in 664 papers matching the search terms, of which 15 papers remained after elimination, based on the specific inclusion and exclusion criteria. In these 15 papers, different MC4R agonists were studied in vivo in animal and human studies. Almost all studies are in the preclinical phase. There are currently no effective clinical treatments for MC4R-deficient obese patients, although MC4R agonists are being developed and are entering phase I and II trials.
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Substantial efforts have been made to develop small molecules as agonists of the MC4 receptor with some limited success.
“Substantial efforts have been made to develop small molecules as agonists of the MC4 receptor with some limited success (61).”
From ACTH Antagonists (2016) · cites this paper as [61]
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- Authors
- Fani, L., Bak, S., Delhanty, P., van Rossum, E. F. C., & van den Akker, E. L. T.
- Affiliations
- Erasmus MC (NL)
- ORCID
- Venue
- International Journal of Obesity
- Published
- 2013-06-18
- Volume
- 38
- Issue
- 2
- Pages
- 163-169
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2019132602
- Cited by
- 121
- References
- 33
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 20 · 2022: 15 · 2021: 6 · 2020: 13 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 12 · 2015: 16 · 2014: 8 · 2013: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- melanocortin-4 receptor, obesity treatment, MC4R agonist, appetite regulation, energy homeostasis, satiety, body weight regulation, pharmacotherapy
- MeSH terms
- Acetamides, alpha-MSH, Animals, Appetite Regulation, Energy Intake, Energy Metabolism, Gene Frequency, Genotype, Humans, Obesity, Peptides, Cyclic, Phenotype, Pyrrolidines, Receptors, Cell Surface, Spiro Compounds, Body Mass Index, Anti-Obesity Agents, Receptor, Melanocortin, Type 4
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