Drug repurposing reveals 29 candidate drugs for brain aging
Our analysis of MR and colocalization has identified 64 druggable genes as potential targets for BAG, suggesting their possible roles in anti-brain-aging mechanisms. By using the drug-gene interaction database, DGIdb, we have identified 466 drugs that are either approved or undergoing clinical development, targeting 29 of the 64 identified genes (Fig. 5AOpens in image viewer and data S22). Notably, 29 drugs (cholecalciferol, diclofenac, didanosine, doconexent, enalapril, esomeprazole, estradiol, fisetin, glycine, hydrocortisone, ibuprofen, indomethacin, ketoprofen, ketorolac, mecamylamine, mefenamic acid, methylene blue, naproxen, nicotine, piroxicam, prasterone, quercetin, resveratrol, sirolimus, stavudine, sulindac, testosterone, dasatinib, and zidovudine) have shown potential in clinical trials for brain aging, as recorded in ChEMBL or reported by researchers (Figs. 1Opens in image viewer and 5BOpens in image viewer). Among these drugs, 20 (dasatinib, diclofenac, didanosine, enalapril, esomeprazole, fisetin, glycine, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, methylene blue, naproxen, piroxicam, quercetin, sirolimus, stavudine, sulindac, and zidovudine) are considered potential geroprotectors, as reviewed by Partridge et al. (32) and Kulkarni et al. (33). Thirteen of these drugs (cholecalciferol, dasatinib, diclofenac, doconexent, estradiol, hydrocortisone, mecamylamine, nicotine, prasterone, quercetin, resveratrol, sirolimus, and testosterone) are associated with clinical trials for aging-related indications, as reported in the ChEMBL database.
In Table S22, there are also some DHP CCBs and statins, but no sartans, metformin, or flozins.