Orphan Receptor of
Nuclear Receptor superfamily is the one with no known endogenous
ligands. Many of these orphan receptors are associated with different types of diseases and therefore deserve special attention to find the potential
ligands they would be associated with. The major task of molecular pharmacology is the deorphanization of the large number of
nuclear receptors with unidentified endogenous agonists. The deorphanization provides a promising research for new
therapeutics. The
Testicular Receptor 4 being negative modulator to other members of the
nuclear receptor superfamily, is one of the Orphan members of this family and is associated with
prostate cancer,
breast cancer,
sickle cell anemia and
joint diseases. The knowledge that related receptors of the same family often have
ligands with similar structural features has helped us to utilize the chemogenomic approach to deorphanize the orphan receptor. Chemogenomics approach involves screening of known
ligands of a
protein family having analogous domain architecture for identification of new leads for existing
protein family members. The deorphanization involved the database homology searching, followed by domain identification, active site prediction, sequence and structure comparative studies. A
ligand library set was prepared based on these studies and was used to deorphanize the receptor. The molecular docking study conducted using PyRx revealed that
estradiol and tretinion as a potential
ligand for
Testicular Receptor 4.