Strategies for design of non peptide CCK1R agonist/antagonist ligands

Curr Top Med Chem. 2007;7(12):1180-94. doi: 10.2174/156802607780960537.

Abstract

This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligands and random screening of diverse compounds, followed by hit optimization. The first group includes: chimeric bifunctional opioid/CCK peptides, designed as opioid agonists with balanced CCK1R/CCK2R antagonist activity for the treatment of neuropathic pain, antagonist and agonist dipeptoids, and 1,3-dioxoperhydropyrido[1,2-c]pyrimidine- and anthranilic acid-based antagonists. Among the ligands derived from random screening, a few new 1,4-benzodiazepine-, 1,5-benzodiazepine-, and five member ring heterocycle-based CCK1R ligands have been reported. Finally, taking into account the importance of receptor mapping studies for ligand optimization and future precise de novo receptor structure-based design of new selective and more effective ligands, the most significant conclusions of these studies have also been reviewed.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Peptides / metabolism
  • Receptors, Cholecystokinin / agonists*
  • Receptors, Cholecystokinin / antagonists & inhibitors*
  • Receptors, Cholecystokinin / metabolism

Substances

  • Ligands
  • Peptides
  • Receptors, Cholecystokinin