Structure-based discovery of a new type of scaffold compound as binding competitors for protein-bound Uremic Toxins.

ABSTRACT: Protein-bound uremic toxins (PBUTs) are the main cause of uremia, but traditional hemodialysis is ineffective in removing them because of their strong ability to bind to human serum albumin (HSA), highlighting the need for new treatments. In this study, first, structure-based docking was used to screen a diverse library of 200,376 virtual compounds against the active sites I and II. After two rounds of docking screening, 3944 candidate molecules were obtained. Second, 23 candidate molecules were obtained after ADMET prediction and toxicity analysis. Five candidate molecules were finally obtained after visual analysis and MM-PBSA calculations. We subsequently assessed their competitive displacement efficiency through a microdialysis experiment, and the results revealed that ZINC000008791789

SUBMITTER: Wang P 

PROVIDER: S-EPMC11568142 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature