Volume 19, Issue 44, July - December, 2025

Natural Compound-Based FLT3 Inhibition in Acute Myeloid Leukemia: A Comprehensive In- Silico Strategy Using Molecular Docking, ADME, and MD Simulation

Zubaer Hossen¹, Md Rezoanul Islam², Md Sajjad Hossain¹, Md. Naim Uddin Forhad², Md Raichul Islam², Abdullah-Al- Jubayer¹, Asura Khanam Lisa¹, Md. Faruk Hasan³, Md. Enamul Haque^1♦

¹Department of Biotechnology and Genetic Engineering, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh
²Department of Biochemistry and Molecular Biology, Gopalganj Science and Technology University, Gopalganj 8100, Bangladesh
³Department of Microbiology, University of Rajshahi, Rajshahi-6205, Bangladesh

^♦Corresponding author
Department of Biotechnology and Genetic Engineering, Faculty of Life Science, Gopalganj Science and Technology University, Gopalganj-8100, Bangladesh

ABSTRACT

Acute myeloid leukemia (AML) with FLT3 mutations is a malignant blood cancer. However, current FLT3 inhibitors used in its treatment have significant side effects and drug resistance problems. Our study aimed to identify relatively safe and effective FLT3 inhibitors from natural phytocompounds to overcome the limitations of current therapies. A total of 2792 phytocompounds were collected from 19 medicinal plants and screened virtually against the FLT3 protein active site. Fifteen top compounds were selected based on docking scores. ADMET analysis and molecular dynamics (MD) simulation were performed to evaluate pharmacokinetics, toxicity, and stability. Three compounds — asperglaucide, 17betahydroxywithanolide K, and withanicandrin — showed strong binding affinities (−9.4, −10.1, and −10.9 kcal/mol, respectively), which were superior to the synthetic inhibitors gilteritinib (−9.1 kcal/mol). ADMET analysis confirmed favorable GI absorption, solubility, and low toxicity, comparable to gilteritinib. The 100-ns MD simulations (RMSD, RMSF, RG, SASA, hydrogen bonds) showed that asperglaucide formed the most stable protein-ligand complex. Natural compounds, especially asperglaucide, have shown promising potential as FLT3 inhibitors for the treatment of AML. Further in vitro and in vivo studies are needed to verify their therapeutic efficacy.

Keywords: Acute myeloid leukemia, FLT3 Inhibitors, Phytocompounds, Molecular Docking, ADMET Analysis, Molecular Dynamics Simulation

Drug Discovery, 2025, 19(44), e21dd3007

PDF / Supplementary 1 / Supplementary 2 / Supplementary 3

Published: 01 October 2025