Scientific Melanogenic effect of dersimelagon (MT-7117), a novel oral melanocortin 1 receptor agonist

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https://onlinelibrary.wiley.com/doi/full/10.1002/ski2.78

Abstract

Background
The activation of melanocortin 1 receptor (MC1R) on melanocytes stimulates the production of eumelanin. A tridecapeptide α melanocyte-stimulating hormone (αMSH) is known to induce skin pigmentation.
Objectives
We characterised the properties of a novel oral MC1R agonist dersimelagon (MT-7117) with respect to its specific binding to MC1R, downstream signalling and eumelanin production in experimental models.
Methods
The competitive binding and production of intracellular cyclic adenosine 3′, 5′-monophosphate in cells expressing recombinant melanocortin receptors were examined. A mouse melanoma cell line B16F1 was used for the evaluation of in vitro melanin production. The in vitro activity of MT-7117 was determined with αMSH and [Nle4, D-Phe7]-αMSH (NDP-αMSH) as reference comparators. The change of coat colour and skin pigmentation were evaluated after repeat administration of MT-7117 by oral gavage to C57BL/6J-Ay/+ mice and cynomolgus monkeys, respectively.
Results
MT-7117 showed the highest affinity for human MC1R compared to the other melanocortin receptors evaluated and agonistic activity for human, cynomolgus monkey and mouse MC1R, with EC50 values in the nanomolar range. In B16F1 cells, MT-7117 increased melanin production in a concentration-dependent manner. In vivo, MT-7117 (≥0.3 mg/kg/day p.o.) significantly induced coat colour darkening in mice. MT-7117 (≥1 mg/kg/day p.o.) induced significant skin pigmentation in monkeys and complete reversibility was observed after cessation of its administration.
Conclusions
MT-7117 is a novel oral MC1R agonist that induces melanogenesis in vitro and in vivo, suggesting its potential application for the prevention of phototoxic reactions in patients with photodermatoses, such as erythropoietic protoporphyria and X-linked protoporphyria.
 

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"Further analysis will be needed to clarify the precise mechanism of agonistic signalling of MT-7117 to learn how it is different from peptide agonists."

"part from pigmentation, various biological effects of endogenous ligand αMSH have been reported in nonclinical settings, such as anti-inflammatory effects,2, 23 anti-fibrotic effects,24, 25 wound healing effects,26 and enhancement of nucleotide excision repair.10, 22 These effects suggest that αMSH plays a broad protective role in homoeostatic maintenance in the body. Future studies will determine if MT-7117 can elicit similar biological effects."

"MT-7117 was less likely to be distributed into the brain, which is the predominant tissue of MC4R expression, in a tissue distribution study in rats (data not shown)."

"NDP-αMSH binds predominantly to MC1R but still behaves as a pan-MCR agonist, which may cause unfavourable side effects such as nausea and this could be explained by its binding to MC3R.14"

I cannot find any impact factor for this journal but i expect it to be very low.
 
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