eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-06-20 23 2 802 811 10.13005/bbra/3540 59346 article Vaishnavi Babasaheb Bagale 1 Rohit Jaysing Bhor 1 Amol Mohan Shirode 2 Pravin Bapurao Jadhav 3 Rutuja Rajendra Lokhande 1 Prasad Jagdish Mantode 1 Department of Pharmaceutical Chemistry, Pravara Rural College of Pharmacy, Ahmednagar, India Department of Pharmaceutical Chemistry, K. B. H. S. S. Trust Institute of Pharmacy, Nashik, India Department of Pharmaceutical Chemistry, Sandip Institute of Pharmaceutical sciences, Nashik, Maharashtra, India. The present investigation focuses on the in-silico evaluation of thiadiazole-based substituted derivatives as potential inhibitors of the 5NQR protein, NUDT5, a promising molecular target associated with breast cancer progression. NUDT5 is involved in nuclear ATP synthesis, chromatin remodelling, and hormone-regulated breast cancer growth, making it an attractive target for anticancer drug discovery. A library of designed compounds (VB1–VB12) was subjected to molecular docking studies to evaluate their binding affinity and interactions within the active site of the target protein. Docking analysis revealed favorable ligand–protein interactions, with binding energies ranging from −8.6 to −10.5 kcal/mol. Among the tested compounds, VB11, VB1, and VB10 exhibited the strongest binding affinities, supported by multiple hydrogen bonds, hydrophobic interactions, and electrostatic interactions with key active-site amino acid residues. Lead compound selection was based on an integrated evaluation of docking affinity, ADMET properties, drug-likeness, and pharmacokinetic suitability rather than docking score alone. Although VB11 and VB1 demonstrated superior docking scores, compounds VB8, VB2, and VB7 showed more favorable overall pharmacokinetic and drug-likeness characteristics, including lower rule violations, improved predicted gastrointestinal absorption, safer CYP inhibition profiles, and balanced physicochemical properties. Physicochemical and drug-likeness analyses indicated that most compounds complied with standard medicinal chemistry parameters, supporting their suitability for further drug development. Based on the combined findings from molecular docking, pharmacokinetic profiling, and drug-likeness evaluation, VB8, VB2, and VB7 were identified as the most promising lead candidates. In this study suggests that thiadiazole derivatives may serve as valuable scaffolds for the development of novel anticancer agents targeting NUDT5 and warrants further in-vitro and in-vivo investigations. https://www.biotech-asia.org/vol23no2/in-silico-design-and-admet-profiling-of-thiadiazole-derivatives-targeting-nudt5-5nqr-for-breast-cancer-therapy/ Abbreviations ADME: Absorption Distribution Metabolism and Excretion ADMET: Absorption Distribution Metabolism Excretion and Toxicity BBB: Blood–Brain Barrier CYP: Cytochrome P450 GI: Gastrointestinal HBA: Hydrogen Bond Acceptor HBD: Hydrogen Bond Donor MR: Molar Refractivity NUDT5: Nudix Hydrolase 5 PDB: Protein Data Bank P-gp: P-glycoprotein TPSA: Topological Polar Surface Area