Development of Novel Melanotropin Ligands for the Prevention and Treatment of Disease
Victor J. Hruby and Minying Cai
MCR Therapeutics, Tucson, Arizona
The five melanocortin receptors and their peptide hormones and neurotransmitter ligands (α-MSH, γ-MSH, ACTH, etc.) which are derived from the primordial precursor protein, proopiomelanocortin (POMC), are involved in most of the biological functions necessary for well-being and survival. These include pigmentation, response to stress, pain, feeding behavior, sexual behavior and function, stress and many others. Thus far, there is only one drug on the market, [Nle4, D-Phe7]-α-MSH (MT-I) a compound we developed over 30 years ago. The native peptides are not selective or very stable which makes their use as drugs difficult. MCR Therapeutics is developing highly receptor selective agonists and antagonist for the melanocortin receptors 1, 3, 4 and 5, that are stable and bioavailable. Applications include skin darkening and protections from U.V. radiation without sun, melanoma cancer detection and treatment, modulation of feeding behavior, sexual behavior and function and others. Recent discoveries and developments for pigmentation (melanoma prevention), melanoma detection and treatment, and application to feeding behavior and sexual function will be discussed.