Melanotan 2 was first synthesized at the University of Arizona. Researchers there knew that one of the best defenses against skin cancer was a natural tan which has been slowly developed over weeks. They hypothesized that an effective way to reduce skin cancer rates in people would be to induce the body’s natural tanning 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 tanning cells (melanocytes) produce the skin’s tanning 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 Hruby, 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, “Melanotan” (later Melanotan I, now known as afamelanotide). They subsequently developed another analog, Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2), which they called “Melanotan 2”. Since their discovery, numerous studies dating back to the mid-1980s have found no obvious toxic effects of the Melanotan peptides. The scientists hoped to use Melanotan peptides to combat melanoma by stimulating the body’s natural tanning 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 eventually lead to skin cancer.