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Melanotan II was first synthesized at the University of Arizona. Researchers there knew that one of the best defenses against skin cancer wasmelanin activated in the skin, a tan. They hypothesized that an effective way to reduce skin cancer rates in people would be to induce the body's natural pigmentary system to produce a protective tan prior to UV exposure. The body's naturally-occurring hormone α-MSH causes melanogenesis, a process by which the skin's pigment cells (melanocytes) produce the skin's pigment (melanin). They tested to see if administering this endogenous hormone to the body directly could be an effective method to cause sunless tanning. What they found was that while it appeared to work, natural α-MSH had too short a half-life in the body to be practical as a therapeutic drug. So they decided to find a more potent and stable alternative, one that would be more practical.
After synthesizing and screening hundreds of molecules, the researchers headed by Victor J. Hruby and Mac E. Hadley, found a peptide, [Nle4,D-Phe7]-α-MSH, that was approximately 1,000 times more potent than natural α-MSH. They dubbed this new peptide molecule "melanotan" (later melanotan-1, now known as afamelanotide). They subsequently developed another analogue, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2), which they called "melanotan II". The scientists hoped to use these peptides to prevent melanoma by stimulating the body's natural pigmentary mechanism to create a tan without first needing exposure to harmful levels of UV radiation. This in turn, they hypothesized, could reduce the potential for skin damage that can possibly lead to skin cancer.
The scientists licensed their patented peptides, via a technology transfer company, to a number of biotechnology companies who intend to develop them into drugs.