Melanotan-2 — Canada Research Brief

Origin and rationale

Melanotan-2 was developed in the 1980s by Victor Hruby, Mac Hadley, and colleagues at the University of Arizona. The original hypothesis was straightforward: if the body's pigmentation signal is α-MSH, a stable cyclic analogue could pre-emptively stimulate eumelanin production and reduce UV-induced skin damage. The compound was designed as a rigidified cyclic lactam to resist enzymatic degradation while preserving receptor affinity.

What the research programme uncovered was that MT-II was not selective: it activated all four melanocortin receptors, and the MC4R activity produced effects on sexual function and appetite that were unexpected from a pigmentation-focused starting point. Those MC4R findings later motivated development of bremelanotide (PT-141), a distinct analogue approved in the US for hypoactive sexual desire disorder.

Research profile

• Pigmentation (MC1R). Activation of MC1R on melanocytes increases eumelanin synthesis in preclinical models.
• Sexual function (MC4R). Central MC4R activation produces erectogenic and libido-related effects — the mechanism that led to PT-141.
• Appetite suppression (MC4R). MC4R is also the receptor that drives the satiety effects observed with melanocortin agonists and that is genetically implicated in human monogenic obesity.

Storage

Store lyophilised Melanotan-2 at −20°C protected from light. Reconstituted peptide is stable refrigerated at 2–8°C for 2–4 weeks.