Strategies for the Design of Non-peptide CCK2 Receptor Agonist and Antagonist Ligands

There has been an effort towards the design and preparation of non-peptide antagonists of the CCK2 receptor going back for over fifteen years. However, as no obvious unmet medical need for this type of molecule has emerged, the interest has somewhat declined. A number of comprehensive reviews have been written where much of the early work is described and so this article focuses on the information generated in the last five years. It is to be hoped that the area will regain some impetus following the recent disclosure of clinical trial data demonstrating the possible utility of a CCK2 antagonist in pancreatic cancer. When considering non-peptide agonists for the CCK2 receptor, traditionally, much less work has been reported in the area. However, recent suggestions of possible clinical utility in the treatment of diabetes, functionally different subtypes of the receptor and molecular models of receptor-ligand interactions should act as a spur for work towards potent small molecule ligands.