Pharmacology review · PMID 39296259

Recommended Tool Compounds for the Melanocortin Receptor (MCR) G Protein-Coupled Receptors (GPCRs) — VialBase Research

Comprehensive characterization of melanocortin receptor subtypes MC1R-MC5R

Last updated · 2024 · Weirath NA, Haskell-Luevano C · ACS Pharmacology & Translational Science
Key findings
  • Comprehensive characterization of melanocortin receptor subtypes MC1R-MC5R
  • Melanotan II is non-selective agonist across MCR subtypes
  • Structure-activity relationships for melanocortin ligands including MT-II
  • MC1R: pigmentation; MC3R/MC4R: energy/sexual function; MC2R: steroidogenesis
  • Recommended tool compounds for research applications

PMID 39296259 — Melanocortin Receptor Tool Compounds

Compound: Melanotan-II Citation: Weirath NA, Haskell-Luevano C. ACS Pharmacol Transl Sci. 2024;7(9):2706-2724. doi:10.1021/acsptsci.4c00129

Summary

Comprehensive pharmacology review of melanocortin receptor subtypes with recommended research tool compounds. Provides structure-activity relationship context for understanding Melanotan II’s non-selective agonism.

Key Points

  • MC1R: Pigmentation (primary MT-II tanning mechanism)
  • MC2R: Steroidogenesis (adrenal; minimal MT-II activity)
  • MC3R: Energy homeostasis, fat distribution
  • MC4R: Appetite, erectile function (target for PT-141)
  • MC5R: Exocrine glands
  • MT-II: Non-selective across MC1R-MC5R, explaining its broad effect profile (tanning + appetite + erections + side effects)

Relevance to Melanotan-II

Explains why MT-II has such a wide range of effects (and side effects) — it hits all five melanocortin receptors. The selectivity advantage of PT-141 (targeting MC3R/MC4R) becomes clear in this pharmacological context.

PubMed

See Also