Figure 1.

Potential for new types of CCK1R-active drugs. Shown is a diagram of a GPCR, highlighting the orthosteric site of action of the natural agonist ligand and distinct allosteric sites of action for allosteric modulators. These can be lateral allosteric modulation through membrane lipids like cholesterol or through association with other membrane proteins, or via ligands that bind to the receptor in places outside of the orthosteric site. Any of these ligands can act as full agonists, stimulating the full range of pleiotropic signaling events activated by the natural agonist, or reduced responses of some of these events (partial agonist and biased agonists). Traditional drug development has focused on full agonists and antagonists (inverse agonists). It is now clear that “texture” in responses can be evoked by allosteric modulation and/or biased agonists.