Melanocortin peptide therapeutics: Historical milestones, clinical studies and commercialization

@article{Hadley2006MelanocortinPT,
  title={Melanocortin peptide therapeutics: Historical milestones, clinical studies and commercialization},
  author={Mac E. Hadley and Robert T. Dorr},
  journal={Peptides},
  year={2006},
  volume={27},
  pages={921-930}
}
Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders
TLDR
Two trials in human volunteers showed that neither MC1R variants nor fair skin reduced the afamelanotide-induced increase in skin pigmentation, and a controlled-release formulation optimizes administration in man and is effective at a lower dose than the daily saline injections.
Intracellular signaling mechanisms of the melanocortin receptors: current state of the art
TLDR
The knowledge of the distinct modulation pattern of MCRs signaling and function may be helpful for the future design of novel drugs able to combine specificity, safety and effectiveness in the course of their therapeutic use.
Development of α-melanocortin analogs for melanoma prevention and targeting.
TLDR
Findings that the physiological α-MSH not only stimulates melanogenesis, but also reduces the extent of DNA damage caused by exposure to solar ultraviolet radiation have further rejuvenated the interest in developing synthetic MC1R agonists for skin cancer prevention.
Melanocortin-4 receptor modulators for the treatment of obesity: a patent analysis (2008-2014).
TLDR
A review of theMC4R patent landscape from 2008 to 2014 is provided and the physicochemical properties of compounds described herein are analyzed to avoid some of the undesirable side effects associated with MC4R activation.
The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology.
  • Y. Tao
  • Biology
    Endocrine reviews
  • 2010
TLDR
A review of the studies on the melanocortin-4 receptor, from its cloning and tissue distribution to its physiological roles in regulating energy homeostasis, cachexia, cardiovascular function, glucose and lipid homeostasi, reproduction and sexual function, drug abuse, pain perception, brain inflammation, and anxiety, is summarized.
Afamelanotide, an agonistic analog of α-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria
  • E. Minder
  • Medicine, Biology
    Expert opinion on investigational drugs
  • 2010
TLDR
Although early, results of the first trials of afamelanotide for PP are promising and the risk–safety profile appears favorable today, it is expected this drug class might prove effectiveness in other medical conditions.
Development of novel frog‐skin peptide scaffolds with selectivity towards melanocortin receptor subtypes
TLDR
Naturally occurring peptides derived from frog skin secretions for selectivity and activity toward melanocortin receptors are investigated and suggest that these frog‐skin peptides could be modified for developing melancortin‐specific ligands and potentially future therapeutics.
Afamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria
TLDR
Based on the high compliance rate and the excellent consistency in clinical effectiveness during six years of compassionate use program in Switzerland, afamelanotide and analogues are expected to become a prospective therapeutic tool.
Bioactive oligopeptides in dermatology: Part I
TLDR
The roles of biologically active short sequence peptides as potential therapeutics through the modulation of collagen, elastin and melanin synthesis are explored through the modulators of collagen synthesis modulators.
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Effects of a potent synthetic melanotropin, Nle4-D-Phe7-α-MSH (Melanotan-I) on tanning: a dose-ranging study
TLDR
An open-label, dose-finding study of a superpotent melanotropic peptide, called Melanotan-I (MT-I), was performed in eight male volunteers with “tannable” skin types III-IV, with no evidence of improved tanning beyond that obtained at the 0.16 mg/kg dose.
Toxicologic studies of a superpotent α-melanotropin, [Nle4, D-Phe7]α-MSH
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This superpotent α melanocyte stimulating hormone (MSH) analog is now entering a Phase I clinical trial with possible therapeutic applications for the treatment of hypomelanotic disorders such as vitiligo and for pharmacologic tanning without the need for sunlight exposure.
Increased Eumelanin Expression and Tanning is Induced by a Superpotent Melanotropin [Nle4-d-Phe7]-α-MSH in Humans¶
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The results show that the tanning induced by MT-I in the face and forearm is associated with a significant increase in the eumelanin content of the human skin.
The Proopiomelanocortin System
TLDR
POMC (31,000 MW) is localized to the pituitary, brain, skin, and other peripheral sites, and MCR antagonists have been used to discover and further delineate other roles of melanocortin ligands.
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TLDR
In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases, suggesting that overall tumor burden was not affected by treatment with the hormone analogue.
A role for the melanocortin 4 receptor in sexual function
TLDR
It is shown that the melanocortin 4 receptor, implicated in the control of food intake and energy expenditure, also modulates erectile function and sexual behavior, and evidence is provided that MC4R-mediated proerectile responses may be activated through neuronal circuitry in spinal cord erectile centers and somatosensory afferent nerve terminals of the penis.
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TLDR
Melanotan-1 can be safely combined with UV-B light or sunlight and appears to act synergistically in the tanning response to light.
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