RORα and RORγ: Promising Drug Targets for Cancer and Inflammation

To identify disease-related targets of CSL, we have compiled a list of the top 10 CSL target proteins (Table 1). Based on the results of docking and the drugbank drug target database, we have identified the ROR family as having the highest affinity. The gscore of RORα, RORβ and RORγ were -9.902, -10.755 and -9.569, respectively. Although their homology is about 68%, their 3D structures are very similar, comprising of 9-11 alpha-helices, stem loops and beta-sheets, and forming a hydrophobic-LBD domain [33].

The ROR subfamily, consisting of RORα, RORβ and RORγ, are widely distributed throughout the tissues of the organism, with most isoforms able to enter the nucleus directly to regulate the transcription of target genes, exhibiting different tissue specificities and participating in different physiological processes. RORα and RORγ are closely associated with the regulation of multiple autoimmune and inflammation-related diseases, with RORγ being a key factor in the differentiation and development of Th17 cells, while RORα is involved in the development of many malignant tumors.

Targeting RORα and its mediated signaling pathways may become a new avenue of anti-tumor therapy, while targeting RORγ inhibition is an important direction for the treatment of inflammatory responses. Hence, RORα and RORγ are the more interesting drug targets according to the drug target database.