Nuclear receptors, Orphanin FQ/nociception, Farnesoid X receptor.
Orphan receptors is a unique resource for discovering novel regulatory systems that impact human health. These provide excellent drug targets for a variety of human diseases. Ligands of nuclear receptors have been used in number of important therapeutic area, such as breast cancers, skin disorders and diabetes. Orphan nuclear receptors; therefore, represent a tremendous opportunity in understanding and treating human diseases. Orphan nuclear receptors using in particular PPARS a strategy for drug discovery in diabetes and obesity, neurodegenerative disease and other related disorders. If an endogenous ligand is there, the orphan receptor is assumed or de-orphaned. An example is the nuclear receptor Farnesoid X receptor (FXR) and the GPCR TGR5/G-protein coupled receptor-19/G protein-coupled bile acid receptor, both of which are activated by bile acids. Adopted orphan receptors in nuclear receptor group contain FXR, liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). One example of an orphan receptor site is the PCP binding site in the NMDA receptor, a type of ligand-gated ion channel. This site is where the recreational drug PCP works, but no endogenous ligand is known to bind to this site. Orphan GPCR exhibited sequence similarities with the opioid receptors. OFQ/N was isolated as its natural ligand and shown to also share sequence similarities to the opioid peptides.