Wholesale Melanotan II — Bulk Research Supply

The names differ by one numeral and the two are confused constantly, but they are structurally and pharmacologically distinct.

Melanotan II is a cyclic heptapeptide — seven residues closed into a ring — and is a nonselective melanocortin agonist, active at MC1R, MC3R, MC4R and MC5R. Melanotan I (afamelanotide) is a linear 13-residue analogue, [Nle⁴, D-Phe⁷]-α-MSH, and is substantially MC1R-selective.

That selectivity difference is the whole reason both are stocked. A pigmentation or photoprotection model wanting MC1R engagement with as little off-target melanocortin activity as possible calls for Melanotan I. A model examining MC4R-mediated central or autonomic signalling calls for Melanotan II, because Melanotan I barely engages it.

Substituting one for the other does not change potency at a shared target — it changes which receptors are in play.

Melanotan II is cyclic, which makes it more conformationally constrained and generally more robust than a linear peptide of similar length. It ships lyophilised and reconstitutes readily in bacteriostatic or sterile water.

Lyophilised material is stored at -20°C and protected from light; reconstituted solution is refrigerated at 2-8°C and used within the study's defined window. These are general laboratory handling notes for a chemical reagent, not directions for human or veterinary use.

Melanotan II is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂. Numbered against α-MSH it covers positions 4 to 10. It keeps the norleucine-4 and D-phenylalanine-7 substitutions of Melanotan I, then swaps Glu⁵ for aspartic acid and Gly¹⁰ for lysine. Those two side chains are joined by an amide — a lactam bridge — that closes a 23-membered ring around the His-D-Phe-Arg-Trp core.

The ring size was an experimental result, not an arbitrary choice. Al-Obeidi, de L. Castrucci, Hadley and Hruby (Journal of Medicinal Chemistry, 1989, 32:2555–2561) used molecular dynamics to design a series of side-chain-to-side-chain lactam analogues and tested seven of them in frog (Rana pipiens) and lizard (Anolis carolinensis) skin bioassays. Analogues with 23-membered rings were reported as roughly 100-fold more potent than α-MSH in the lizard assay and selective for lizard over frog melanocyte receptors; shifting the ring away from 23 atoms lost potency, and only the 23- and 24-membered rings showed prolonged residual activity.

That cyclization explains most of the practical contrasts with Melanotan I. Melanotan II has seven residues rather than thirteen, is conformationally constrained rather than freely flexible, and weighs 1,024.18 g/mol against 1,646.85.

Melanotan II matters to melanocortin research partly because two heavily used molecules were built on the same scaffold.

SHU9119 keeps the lactam ring and replaces D-phenylalanine at position 7 with D-2'-naphthylalanine. That one substitution converts the agonist into an antagonist at MC3R and MC4R. Fan, Boston, Kesterson, Hruby and Cone used the pair together in Nature in 1997 (385:165–168): in that work, Melanotan II delivered intracerebroventricularly inhibited feeding in four rodent models of hyperphagia, co-administered SHU9119 blocked that inhibition completely, and SHU9119 given alone increased nocturnal and post-fast feeding. The paper reported SHU9119 IC₅₀ values of 0.36 nM at MC4R and 4.5 nM at MC3R. The MTII/SHU9119 pair became a standard agonist–antagonist set in central melanocortin work.

Bremelanotide (PT-141) differs from Melanotan II at one atom-level detail: the C-terminal lysine ends in a free carboxylic acid rather than an amide. Cayman Chemical's product documentation gives its formal name as N-acetyl-L-norleucyl-L-α-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysine (2→7)-lactam, formula C₅₀H₆₈N₁₄O₁₀, against C₅₀H₆₉N₁₅O₉ for Melanotan II. Bremelanotide was approved by the FDA as Vyleesi on 21 June 2019. Melanotan II itself has never been approved by any regulator, and the UK MHRA has warned publicly since 2008 that melanotan products offered online are unlicensed and that their safety, quality and effectiveness have not been verified. The first published human exposure to Melanotan II was a three-volunteer pilot study by Dorr et al. (Life Sciences, 1996, 58:1777–1784).

Cyclic peptides in a catalog like this one are closed in two quite different ways, and Melanotan II sits on the less fragile side of that split.

Its ring is a lactam — an amide bond between the Asp⁵ side-chain carboxyl and the Lys¹⁰ side-chain amine, chemically the same kind of bond as the peptide backbone itself. It is not a disulfide. Disulfide-closed peptides open under reducing conditions, so a reagent such as dithiothreitol or 2-mercaptoethanol in a buffer will linearize them; Melanotan II's ring is indifferent to those reagents, because there is no cysteine in the molecule to reduce. Its formula, C₅₀H₆₉N₁₅O₉, carries no sulfur at all.

That has two practical consequences. Redox-containing assay buffers that would compromise a disulfide-bridged peptide do not open this ring, and the constrained conformation the 1989 ring-size work selected for is retained under those conditions. The flip side is that the ring also cannot be opened deliberately as a control, so a linear comparator has to be a separately synthesized peptide rather than a reduced aliquot of the same vial.