Melanotan I

Melanotan I (Afamelanotide) Research Standard

Melanotan I (CAS 75921-69-6), also indexed as afamelanotide and NDP-α-MSH, is the linear α-MSH analogue [Nle⁴, D-Phe⁷]-α-MSH. Supplied as a 10 mg lyophilized powder in a 3 mL vial, it is the compound the melanocortin field uses as its high-potency linear reference — the analogue against which subtype-selective candidates are benchmarked.^[1]

Mechanism of Action & Research Context

The molecular targets are the melanocortin receptors, five class A GPCRs signalling through G_s and cyclic AMP.

• Potent at nearly every subtype. NDP-α-MSH possesses nanomolar efficacies at all melanocortin receptor subtypes except MC2R — the ACTH receptor, which the melanocortin peptides do not engage. That near-universal potency is precisely what makes it a reference rather than a selective tool.^[1]

• Two substitutions, both deliberate. Norleucine at position 4 removes the oxidation-prone methionine of native α-MSH; D-phenylalanine at position 7 inverts a stereocentre in the message sequence. Together they give a linear peptide with markedly greater potency and stability than the parent hormone.

• Linear, where MT-II is cyclic. Melanotan I has no macrocycle. Comparing it against cyclic analogues such as MT-II isolates what conformational constraint contributes, separately from residue substitution.^[4]

• Five receptors, not one. The melanocortin family comprises MC1R–MC5R, class A GPCRs coupling to G_s, adenylyl cyclase and cyclic AMP. cAMP accumulation is the standard functional readout, and real-time luminescent cAMP reporters in receptor-expressing HEK293 lines are an established platform for quantifying it.^[5]

• The message sequence engages subtypes differently. Systematic truncation of NDP-α-MSH established that the conserved His-Phe-Arg-Trp core does not bind and stimulate each subtype in the same fashion, overturning the earlier assumption of a shared binding mode.^[1]

• Residue chemistry drives selectivity. In α-MSH/γ-MSH hybrid series, increasing hydrophobicity and substituting bulkier aromatic residues at positions 6 and 8 separates MC1R-preferring from MC3R-preferring analogues.^[3]

Research Applications

Primary fields of in vitro and preclinical laboratory investigation include:

• Receptor binding panels across MC1R–MC5R with a high-potency linear anchor.^[2]

• cAMP functional assays benchmarking G_s-coupled output.^[5]

• Structure-activity relationship work comparing linear against cyclic scaffolds.^[3,4]

• Comparative pharmacology against native α-MSH, ACTH and the endogenous antagonist AgRP.^[2]

Analytical Documentation

Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.

References

1. Haskell-Luevano C, Hendrata S, North C, et al. Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC1R and MC4R. J Med Chem. 1997;40(14):2133–2139. doi:10.1021/jm960840h
2. Schiöth HB, Muceniece R, Wikberg JE. Characterization of the binding of MSH-B, HB-228, GHRP-6 and 153N-6 to the human melanocortin receptor subtypes. Neuropeptides. 1997;31(6):565–571. doi:10.1016/s0143-4179(97)90002-0
3. Cai M, Mayorov AV, Cabello C, et al. Novel 3D pharmacophore of alpha-MSH/gamma-MSH hybrids leads to selective human MC1R and MC3R analogues. J Med Chem. 2005;48(6):1839–1848. doi:10.1021/jm049579s
4. Bednarek MA, MacNeil T, Tang R, et al. Potent and selective agonists of human melanocortin receptor 5: cyclic analogues of alpha-melanocyte-stimulating hormone. J Med Chem. 2007;50(10):2520–2526. doi:10.1021/jm0614275
5. Pantel J, Williams SY, Mi D, et al. Development of a high throughput screen for allosteric modulators of melanocortin-4 receptor signaling using a real time cAMP assay. Eur J Pharmacol. 2011;660(1):139–147. doi:10.1016/j.ejphar.2011.01.031

Storage & Handling

Store at controlled room temperature, sealed and protected from light.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.

Related Research Compounds

• Melanotan II
• SNAP-8
• UNII-6Y24O4F92S
• SM04554

Research Use Only Disclaimer: This product is labeled and sold "For Research Use Only - NOT FOR HUMAN CONSUMPTION." It is not a drug, dietary supplement, food, cosmetic, or medical device, and it is not approved by the FDA or any other regulator for human or veterinary use. It is supplied to approved account holders as a research chemical for laboratory use and must be handled in accordance with applicable law.