Design of novel melanocortin receptor ligands: multiple receptors, complex pharmacology, the challenge

Eur J Pharmacol. 2011 Jun 11;660(1):88-93. doi: 10.1016/j.ejphar.2010.10.109. Epub 2011 Jan 3.

Abstract

The major pharmacophore for the melanocortin 1, 3, 4 and 5 receptors is the sequence -His-Phe-Arg-Trp-. There is a need for potent, biologically stable, receptor selective ligands, both agonists and antagonists, for these receptors. In this report we briefly examine the structural and biophysical approaches we have taken to develop selective agonist and antagonist ligands that can cross (or not) the blood brain barrier. Remaining questions and unmet needs are also discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drug Design*
  • HEK293 Cells
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Receptors, Melanocortin / agonists
  • Receptors, Melanocortin / antagonists & inhibitors
  • Receptors, Melanocortin / metabolism*
  • Small Molecule Libraries / metabolism
  • Small Molecule Libraries / pharmacology
  • Substrate Specificity
  • alpha-MSH / chemistry
  • alpha-MSH / metabolism
  • alpha-MSH / pharmacology

Substances

  • Ligands
  • Receptors, Melanocortin
  • Small Molecule Libraries
  • alpha-MSH