Melanotan II



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Product Name:Melanotan II

Cas No:121062-08-6

Molar Mass:1024.00

Chemical Formula:C50H69N15O9


Storage:Store at -20°C

Sequence: XDHFRWK

Target Indicators: Melanotan II (MT II) is a synthetic analogue of α-melanocyte-stimulating hormone that, via interaction with the melanocortin 1 receptorStore at -20°C

Target:melanocortin receptor


Application: Melanotan II is a synthetic peptide analog of the melanocortin hormone alpha-melanocyte-stimulating hormone (α-MSH). It is primarily known for its ability to induce skin pigmentation through the stimulation of melanocytes, leading to increased production of melanin. In pharmaceutical chemistry, Melanotan II is studied for its potential therapeutic applications in treating conditions such as erythropoietic protoporphyria (EPP) and other photosensitivity disorders, where increased skin pigmentation provides protection against sunlight-induced skin damage. Additionally, it is investigated for its potential role in appetite suppression and weight loss due to its effects on reducing food intake through central melanocortin receptors. Melanotan II’s mechanism of action in stimulating melanogenesis and regulating appetite makes it a subject of interest in dermatology, endocrinology, and obesity research.

 Current Research: Melanotan II (MT-II) is a cyclic peptide derived from α-melanocyte-stimulating hormone (α-MSH), which has gained attention for its therapeutic potential in various conditions, including sexual desire disorders and erythropoietic protoporphyria. MT-II belongs to a class of cyclic peptides, known for their improved properties over linear counterparts, such as increased binding affinity, selectivity towards targets, metabolic stability, and enhanced cell permeability. The development of MT-II and similar peptides has been facilitated by advances in peptide cyclization strategies, including chemical linkage of peptide onto scaffolds (CLIPS). CLIPS technology involves halogenated scaffolds reacting with thiol groups of cysteine and cysteine derivatives, resulting in conformationally constrained peptides with enhanced stability and biological activity.


The melanocortin transduction system (MCTS), consisting of five receptors (hMC1R–hMC5R), has emerged as a promising therapeutic target for conditions like obesity, cancer-related weight loss, and sexual dysfunction. Synthetic agonists and antagonists targeting melanocortin receptors (MCRs) have been developed through medicinal chemistry efforts, with MT-II serving as a lead scaffold for structure-activity relationship (SAR) studies. These studies have led to the identification of setmelanotide, a selective agonist for hMC4R approved for the treatment of genetic childhood-onset obesity.


Recent research has focused on enhancing the selectivity and potency of MCR ligands through peptide modification and cyclization strategies. A small library of MT-II analogues was synthesized by replacing the lactam bridge with xylene-derived thioethers of varying sizes and steric hindrances. These cyclic peptides displayed nanomolar to sub-micromolar affinity towards MCRs, with certain derivatives showing improved selectivity profiles compared to MT-II. Computational modeling elucidated the structural basis for the observed differences in receptor affinity and selectivity, highlighting the potential of CLIPS-based cyclization to generate diverse chemotypes with varying degrees of receptor interaction.


In summary, Melanotan II and its analogues represent a class of cyclic peptides with therapeutic potential for diverse conditions. Through innovative cyclization strategies like CLIPS, these peptides can be optimized for improved pharmacological properties, paving the way for the development of selective and effective treatments targeting the melanocortin transduction system and beyond.

Reference: Tomassi, S., Dimmito, M. P., Cai, M., D’Aniello, A., Del Bene, A., Messere, A., … & Di Maro, S. (2022). CLIPSing melanotan-II to discover multiple functionally selective hMCR agonists. Journal of Medicinal Chemistry, 65(5), 4007-4017.

Peters, B., Hadimeri, H., Wahlberg, R., & Afghahi, H. (2020). Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN case reports, 9(2), 159-161.

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