The glyoxalase system plays a crucial role in detoxifying methylglyoxal, a reactive metabolite linked to various diseases, including cancer and diabetes. Glyoxalase I (GlxI) has been identified as a promising drug target due to its overexpression in pathological conditions. This study employs an in silico approach to repurpose FDA-approved drugs as potential GlxI inhibitors. A virtual screening of approximately 2500 FDA-approved drugs was conducted using molecular docking, followed by molecular dynamics (MD) simulations to assess stability and interaction dynamics. Trilaciclib and Olmesartan emerged as strong inhibitors of GlxI, exhibiting stable binding and high binding free energies. Additionally, these drugs showed potential as dual inhibitors by also binding to Glyoxalase II (GlxII). The results highlight the feasibility of drug repurposing to accelerate the discovery of novel therapeutic agents. Further experimental validation is necessary to confirm these findings and explore their clinical applications.
