RORα and RORγ: Promising Drug Targets for Inflammatory Diseases and Cancer

To identify disease-related targets of CSL, we have listed the top 10 CSL target proteins in Table 1. Based on the results of docking and the DrugBank drug target database, we have screened 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, and they are composed of 9~11 alpha-helices, stem loops, and beta-sheets, forming a hydrophobic-LBD in the domain [33]. However, whether they are functionally identical or selective for the recognition of the same small-molecule compound needs to be explored in-depth [34].

RORs have three members in the subfamily - RORα, RORβ, and RORγ - which are widely distributed throughout the tissues of the organism. Most isoforms can 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 important regulators of multiple immune functions and are closely associated with the regulation of multiple autoimmune and inflammation-related diseases. RORγ is a key factor in the differentiation and development of Th17 cells, while RORα is involved in the development of many malignant tumors, including liver cancer, breast cancer, glioma, and colorectal cancer. Therefore, studying agonists of RORα and targeting RORγ inhibition is an important direction for the treatment of inflammatory diseases and malignancies [36, 37].

According to the drug target database, RORα and RORγ are the more interesting drug targets [38].