In Silico Identification of Promising PDE5 Inhibitors Against Hepatocellular Carcinoma among recently FDA approved drug: A Docking and ADMET Study

Abstract

Introduction: Hepatocellular Carcinoma (HCC) is a prevalent and deadly form of liver cancer. Phosphodiesterase 5 (PDE5) inhibitors, known for treating erectile dysfunction, have shown potential as anti-cancer agents due to their effects on cellular signaling pathways cGMP. This study explores the repurposing of recently FDA-approved drugs as PDE5 inhibitors for HCC treatment through in silico analysis.

Objectives: The primary objectives were to identify potential PDE5 inhibitors from the pool of newly approved FDA drugs, evaluate their binding affinities to the PDE5 enzyme (cGMP), and predict their ADMET profiles to assess suitability for HCC treatment.

Methods: We employed molecular docking studies to simulate the binding of drugs to the PDE5 enzyme. Subsequently, we conducted in silico ADMET profiling to evaluate the pharmacokinetic properties and potential toxicity of the compounds.

Results: Several FDA approved compounds demonstrated strong binding affinities to PDE5, suggesting potential efficacy in HCC treatment. The ADMET profiles indicated favorable pharmacokinetic properties and a low risk of toxicity for the top candidates.

Conclusions: The study identified promising candidates for PDE5 inhibitors among recently approved drugs, with potential applications in HCC treatment. These findings warrant further experimental validation and clinical trials to confirm their efficacy and safety in a therapeutic context.