Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases

Summary

This is a narrative review, not an original study, and it contains no new data on PT-141. It summarizes the function and genetic polymorphism of the melanocortin receptors (MCRs), the regulatory pathways involving them, and evidence for their role in inflammatory responses and their potential therapeutic use in inflammatory diseases. MCRs are involved in skin pigmentation, appetite, stress response and cognition, steroid synthesis, energy balance, cellular regeneration and immune regulation, and are found in tissues ranging from the brain, limbic system and adrenal cortex to neutrophils, monocytes and macrophages.

Key Findings

• Gene mutations in MC1R, MC2R, MC3R and MC4R are associated with risk of melanoma, familial glucocorticoid deficiency, obesity and type 2 diabetes, respectively
• MC1R, MC2R and MC5R genes are involved in the risk of major depressive disorder
• MCRs are involved in inflammatory disorders including atopic dermatitis, autoimmune uveitis, sarcoidosis, respiratory diseases, multiple sclerosis, scleroderma, inflammatory bowel disease, ALS, Alzheimer’s disease, arthritis and reperfusion injury
• Alpha-MSH analogs play a role in atopic dermatitis and scleroderma, and the MC1R agonist dersimelagon has shown effectiveness in systemic sclerosis
• The FDA has approved repository corticotropin injection (RCI) for sarcoidosis
• FDA-approved melanocortin agonists include bremelanotide for hypoactive sexual desire disorder, afamelanotide for erythropoietic protoporphyria, and setmelanotide for obesity due to pro-opiomelanocortin or leptin receptor deficiency

Relevance to PT-141

PT-141 (bremelanotide) appears here only as one of the FDA-approved melanocortin agonists, approved for hypoactive sexual desire disorder. The review is useful background on the melanocortin receptor family that agonists like bremelanotide act on, and on the wider roles of melanocortin receptors in appetite, energy balance and inflammation. It does not report new trials, dosing or safety data for PT-141.

Citation

Bardhan M, Anand A, Javed A, et al. Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases. Diseases. 2025;13(9):305. doi:10.3390/diseases13090305. PMID: 41002740

See Also

• Parent compound: PT-141
• Related compound: Melanotan-II