What Is MT2 (Melanotan 2)?

The melanocortin system consists of five seven-transmembrane spanning G-protein coupled (GPCRs) receptors (MC1R-MC5R), the endogenous agonists a-, B- and melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and the endogenous antagonists Agouti and Agouti-related protein (AGRP).

The melanocortins are a group of small protein hormones derived by post-translational cleavage of the proopiomelanocortin (POMC) gene product. The known melanocortin hormones include alpha-melanocyte stimulating hormone (MSH), beta-MSH, gamma-MSH and adrenocorticotropic hormone (ACTH). Five melanocortin receptors (MC1R through MC5R) have been identified and most of these show tissue-specific expression patterns, as well as different binding affinities for each of the melanocortin hormones.

The central melanocortin system consists of alpha-MSH, agouti-related protein (AGRP), MC3R and MC4R. AGRP and alpha-MSH are believed to be the natural antagonist and agonist respectively of MC3R and MC4R. This central melanocortin system is thought to play a fundamental role in the control of feeding and body weight.

Knock-out mice models and genetic studies have pointed to the importance of the melanocortins in complex human pathways such as pigmentation, lipolysis, food intake, thermogenesis, sexual behavior, memory and inflammatory response.

Recently the melanocortins and their receptors have been the target for drug-based treatment of human physiological processes. MC3R and MC4R are likely targets for controlling body weight; MCIR may be used in the treatment of inflammation and MC2R for the treatment of glucocorticoid deficiency. A role for MC5R still remains unclear, but the evidence suggests an exocrine gland function. Melanotan II is a synthetic cyclic lactam analog of naturally occurring α-MSH (Melanocyte-stimulating hormone), a truncated version of melanotan I (afamelanotide) with a longer half-life. Melanotan I [Nle4,D-Phe7] α-MSH is a potent non-selective analog of α-MSH with activity at the MC1R, MC3R, MC4R, and MC5R receptors and good in vivo stability and biodistribution, but poor blood–brain barrier permeability. Melanotan II (MTII), Ac-Nle-c[Asp5, DPhe7,Lys10] α -MSH-NH2, is of similar potency and range of effects as MTI but enhanced in vivo stability (T1/2: 1–2 h) and blood–brain barrier permeability because of its cyclic structure.

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