1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
*Corresponding Author: Sumaih A. Alnowihi - nd9995610@gmail.com
Background: The apolipoprotein E4 (APOE4) isoform is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) due to its pathological structural conformation that mainly contributes to amyloid aggregation and tau hyperphosphorylation. Indeed, numerous research interests in APOE4, which may lead to a loss of function, have led this study to focus on stabilizing APOE4 using small molecules, using bioinformatics tools to identify the appropriate drug that restores the protein to its normal function.
Methods: We used the PyRx program for docking to select the compound with the highest binding affinity to the N-terminal APOE4 protein and the APOE4 protein generated by AlphaFold.
Results: While several compounds demonstrated favourable binding to N-terminal or APOE4, one drug selected as a candidate exhibited a superior combination of binding affinity.
Conclusion: We observed that 3-(2-phenylphenoxy)-1,2-benzothiazole 1,1-dioxide (CID 892507) was highest binding affinity in two proteins, and its binding with critical residues in the protein that play a role in stabilization. This finding enhances the application of various tests to ensure its efficacy and safety as a corrector drug for APOE4 in the treatment of Alzheimer's disease.
Keywords: APOE4, Alzheimer's disease, molecular docking, small molecule stabilizer, in silico screening, PyRx, AlphaFold.
How to cite this article: Alnowihi SA, Alshubaily FA, Albishi H. In Silico Identification of Small Molecule Stabilizers of APOE4 for Alzheimer's Disease Therapy. Int J Drug Deliv Technol. 2026;16(9s): 28-37; DOI: 10.25258/ijddt.16.9s.4
Source of support: None
Conflict of interest: None