MT-2 — 10 mg

A cyclic α-MSH analogue and non-selective agonist at several melanocortin receptors, used as a reference compound in in-vitro studies of melanocortin signalling and cellular melanogenesis. 10 mg vial, lyophilized powder, ≥99% HPLC purity verified by third-party analysis. For laboratory research use only.

Research areas

• MC1R / MC3R / MC4R / MC5R signalling in vitro
• Melanogenesis in cell culture (cAMP → MITF → tyrosinase pathway)
• Comparative pharmacology of cyclic and linear melanocortin agonists

Technical data

MT-2, MT-I, afamelanotide: three names, two different molecules

This is the most widespread confusion in this family, and a single number settles it.

MT-I and afamelanotide are the same molecule: [Nle⁴, D-Phe⁷]-α-MSH, usually abbreviated NDP-MSH — a linear 13-amino-acid peptide of roughly 1,646 Da, reproducing the full length of α-MSH with two substitutions that slow enzymatic degradation. Under the name afamelanotide it holds a marketing authorisation for a rare and very narrow indication, under strict hospital supervision.

MT-2 is something else: a cyclic heptapeptide of roughly 1,024 Da, closed by a lactam bridge between the Asp and Lys side chains. It retains the His-D-Phe-Arg-Trp motif, the pharmacophore core common to melanocortins, but not the peripheral residues of α-MSH.

The verifiable criterion is therefore molecular mass: ≈ 1,024 Da for MT-2, ≈ 1,646 Da for MT-I. A COA that does not specify the form (cyclic or linear) does not tell you what is in the vial.

The second point matters even more: MT-2 is not selective. It activates MC1R, MC3R, MC4R and MC5R with potencies of the same order of magnitude; only MC2R, the ACTH receptor, is largely out of reach. Direct methodological consequence: in an integrated model, no read-out obtained with MT-2 can be assigned to a single receptor. Protocols aiming to isolate one receptor subtype use selective tools, not MT-2. MT-2's legitimate role is as a pan-melanocortin positive control.

Mechanism studied

The five melanocortin receptors (MC1R–MC5R) are class A G-protein-coupled receptors, canonically coupled to Gαs. Activation stimulates adenylate cyclase, raises intracellular cAMP and activates protein kinase A. In melanocyte models in vitro, this cascade phosphorylates CREB, induces MITF, and drives transcription of the melanin pathway enzymes — chiefly tyrosinase, the rate-limiting step — measured by cAMP assay, tyrosinase activity or cellular melanin content.

For the other subtypes the literature describes distinct roles, largely established in rodent models and by genetics: MC3R and MC4R, expressed in the central nervous system, are involved in energy homeostasis; MC5R is associated with exocrine gland function. The central melanocortin system is also under the control of an endogenous antagonist, AgRP — a reminder that this circuit is bidirectionally regulated, not driven by simple agonism.

What the literature shows

What is solidly established concerns receptor pharmacology: affinity and efficacy profiles of MT-2 across melanocortin receptor subtypes in recombinant systems, cAMP responses, and the role of the lactam ring's conformational constraint. As such, MT-2 is a documented and frequently used comparator.

What the literature does not show must be stated just as plainly. There is no large randomised clinical trial establishing a safety profile for MT-2 in humans, and no marketing authorisation anywhere. Human data are limited to small, early studies and to a case-report literature from dermatology and toxicology, collected after the fact on uncontrolled exposures. That literature describes changes in naevi — darkening, new pigmented lesions — and melanoma cases reported after exposure to products of this family sold outside controlled channels, along with acute systemic effects consistent with the molecule's non-selectivity. A further problem is product identity: analyses of such preparations have shown highly variable content, incorrect labelling and contamination, so part of the reported effects cannot even be attributed to the peptide with certainty.

Regulatory status and public warnings

MT-2 is not authorised as a medicine in any jurisdiction. Several national health agencies — in the United Kingdom, in several Nordic countries, in Australia, among others — have issued public warnings against products of this family sold outside controlled channels and against their use outside a medical or laboratory setting, citing the absence of any benefit-risk evaluation, the reported adverse effects, and the unknown pharmaceutical quality of circulating preparations. European safety notifications have targeted products of this type.

This reference is accordingly offered solely as a laboratory reagent, to qualified teams, for in-vitro work and experimental models. No effect outside the experimental setting is described, claimed or implied by NEXUS.

Reconstitution: a worked example

With 2 mL of bacteriostatic water in a 10 mg vial: 10 mg ÷ 2 mL = 5 mg/mL, i.e. 5,000 mcg/mL. On a U-100 syringe, 10 IU = 0.1 mL = 500 mcg, giving 20 draws per vial.

The most common trap: the volume of water never changes how much peptide is in the vial. Only the volume to draw changes. Our reconstitution calculator computes any other combination live.

Add the solvent slowly down the vial wall, then swirl gently. No vigorous shaking, no vortex — shear denatures peptides.

Storage

Lyophilized powder: -20 °C or below, protected from light and moisture; stable for years when unopened. After reconstitution: 2–8 °C, protected from light, with a reference shelf life of 28 days. For longer storage, frozen aliquots are preferable to repeated freeze-thaw cycles.

Common laboratory mistakes

• Confusing MT-2 with MT-I / afamelanotide. Two distinct molecules: a ≈ 1,024 Da cyclic heptapeptide versus a ≈ 1,646 Da linear 13-mer. Check molecular mass on the COA before applying a published result.
• Assigning a read-out to MC1R alone. MT-2 also activates MC3R, MC4R and MC5R. Without a selective tool in parallel, no single-receptor conclusion holds.
• Using plain sterile water for a multi-draw vial. Without a preservative, the solution is no longer protected once the stopper has been pierced several times.
• Vortexing the vial. Vigorous agitation denatures peptides.
• Repeatedly refreezing the reconstituted solution. Each cycle degrades a fraction of the peptide.