To identify potential for new pharmacological treatments of OA through drug repurposing or compound development, we examined OPRM1, PPP6C, and FURIN across multiple drug repurposing databases (the Drug Gene Interaction Database v.3.0 [DGIdb]44, Connectivity Map [CMap]45, PHAROS [https://pharos.nih.gov/]46). OPRM1 is a known target of more than one-hundred drugs and compounds, including illicit drugs, abused therapeutics (e.g., oxycodone), and OA treatments (e.g., methadone and buprenorphine) (Supplementary Table 17a–c). In contrast, PPP6C is not a target of any known drug or compound but has a 94% likelihood that its protein has ligand properties based on its chemistry47. FURIN is the target of one approved drug, pirfenidone, which is indicated for treatment of idiopathic pulmonary fibrosis. There are more than 80 compounds identified targeting FURIN, most developed as inhibitors targeting FURIN function in infectious diseases (Supplementary Table 18a–c).
