Bioactive small compounds effectively inhibit ChREBP overexpression to treat NAFLD and T2DM: A computational drug development approach

• DOI: 10.1016/j.heliyon.2025.e42477
• Publication Date: 2025-02-10T15:19:38Z
• Authors: Hiron Saraj Devnath; Maisha Maliha Medha; Md Naharul Islam; Partha Biswas; Debasree Sen Oisay; Arafat Hossain; Rubaet Sharmin Ema; Md Mohaimenul Isl...; Mimi Golder; Md Nazmul Hasan; Biswajit Biswas; Samir Kumar Sadhu
• Keywords: Drug Development; Carbohydrate-responsive element-binding protein

A glucose-dependent carbohydrate-signaling gene regulator named Carbohydrate response element binding protein (ChREBP), has recently been discovered as a major metabolic of enzymes involved in the progression non-alcoholic fatty liver disease (NAFLD) and type-II diabetes mellitus (T2DM). As result, this research is aimed to identify natural small molecules drug candidates that target ChREBP order counter aggressive NAFLD T2DM. comprehensive silico design strategy was implemented find possible inhibitors targeted protein. site-specific molecular docking approach used screen 20 FDA approved anti-diabetic drugs 494 phytochemicals from sources against ChREBP, top ten compounds were selected for further studies based on their affinities. The ADME toxicity profiles demonstrated efficacy safety. result MD simulations protein–ligand complex structures indicated stability potential activity. data screening process following docking, ADMET properties, simulation approaches, five (dieckol, isocorilagin, stachyurin, stachysetin thonningianin A) with favorable values which indicates strong promising effective treatment T2DM.Graphical abstract