Building on endogenous lipid mediators to design synthetic receptor ligands

Large numbers of diverse biologically active molecules are produced from phospholipids, the constituents of biological membranes. Indeed, many lipid-derived ligands, which can undergo inter-transformation between one and another by certain kinases or enzymes, bind to protein receptors such as G-protein-coupled receptors, and serve to regulate multiple biological processes through a variety of signaling pathways. Thus, lipid mediators are likely involved in a synergistic regulatory network, and dysfunction of this network may result in diseases. Here, we reviewed recent progress in the drug development targeting related receptors, focusing on the identification of common structural features which can both come from endogenous ligands or artificial ligands. We also discussed how these features have been utilized in drug design and relevant issues such as potency, selectivity, metabolic stability, and toxicity.