Virtual Screening and Experimental Validation of Mitoxantrone's Potential as a DNMT1 Inhibitor in T-ALL

DOI

10.2991/978-94-6463-829-5_18How to use a DOI?

Keywords

T-ALL; DNMT1; Virtual screening; Mitoxantrone; Drug repurposing

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological malignancy. Current treatment options, including chemotherapy and targeted therapies, are limited in efficacy for certain patients, underscoring the urgent need for novel therapeutic strategies. Recent studies have highlighted a pivotal role of DNA methyltransferase 1 (DNMT1) in the pathogenesis of T-ALL, suggesting it as a promising therapeutic target. In this study, we utilized integrative multi-omics analyses to evaluate the therapeutic potential of DNMT1. A structure-based virtual screening of FDA-approved compounds from the ZINC20 database was conducted using the Glide module in sequential modes: high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). The binding affinities of the docked compounds were further refined using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) scoring. Based on docking scores and binding interactions, Mitoxantrone and Hexoprenaline were identified as candidate DNMT1 inhibitors. Experimental validation showed that Hexoprenaline had no significant effect on T-ALL cell proliferation, whereas Mitoxantrone significantly suppressed T-ALL cell growth and reduced global genomic DNA methylation levels. These findings provide new therapeutic insights for T-ALL, particularly through drug repurposing of approved agents, potentially reducing the cost and time associated with drug development. Further clinical investigation is warranted to assess the safety and efficacy of these DNMT1-targeting agents in T-ALL treatment.

Copyright

© 2025 The Author(s)

Open Access

Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

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TY  - CONF
AU  - Jiaqi Deng
AU  - Zhuoyu Cui
AU  - Qiaowen Huang
AU  - Xingyu Zhou
AU  - Yu Lu
AU  - Tong Zhang
AU  - Xiaoyu Zhang
PY  - 2025
DA  - 2025/08/28
TI  - Virtual Screening and Experimental Validation of Mitoxantrone's Potential as a DNMT1 Inhibitor in T-ALL
BT  - Proceedings of the 2025 International Conference on Chemical Engineering and Biological Science (CEBS 2025)
PB  - Atlantis Press
SP  - 156
EP  - 167
SN  - 2352-5401
UR  - https://doi.org/10.2991/978-94-6463-829-5_18
DO  - 10.2991/978-94-6463-829-5_18
ID  - Deng2025
ER  -