Identifying DE19725241 as a Novel FTO Potential Inhibitor for Treating Pancreatic Cancer with an Active Learning Model and Molecular Dynamics Simulations based on Chemical Space Library Data

Xu, Yunyun; Zhou, Yucheng; Jian, Peng

doi:10.3389/fchem.2025.1529278

ORIGINAL RESEARCH article

Front. Chem.

Sec. Theoretical and Computational Chemistry

Volume 13 - 2025 | doi: 10.3389/fchem.2025.1529278

This article is part of the Research Topic Dynamics and Functional Exploration of Pharmacologically Active Proteins View all 3 articles

Identifying DE19725241 as a Novel FTO Potential Inhibitor for Treating Pancreatic Cancer with an Active Learning Model and Molecular Dynamics Simulations based on Chemical Space Library Data

Provisionally accepted

Yunyun Xu ^*

Yucheng Zhou

Peng Jian

Hangzhou Medical College, Hangzhou, China

The final, formatted version of the article will be published soon.

This study investigates the identification of DE19725241 as a potent inhibitor of fat mass and obesity-associated protein for pancreatic cancer treatment. Using active learning models and molecular dynamics simulations, we screened over 22 million compounds and identified DE19725241 as a top candidate based on its superior binding affinity and stability. The molecular dynamics simulations revealed that DE19725241 exhibited consistent interactions with critical binding residues, including ARG-96, TYR-108, and GLU234, with lower RMSD fluctuations compared to FB23. Moreover, free energy calculations showed that DE19725241 achieved a highly stable binding configuration with an MMGBSA binding free energy of -63.13 kcal/mol. These findings highlight the significant potential of DE19725241 for clinical applications, warranting further experimental validation.

Keywords: FTO inhibitor, Pancreatic Cancer, chemical space library, Active Learning Model, Molecular Dynamics Simulation

Received: 16 Nov 2024; Accepted: 27 Feb 2025.

Copyright: © 2025 Xu, Zhou and Jian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yunyun Xu, Hangzhou Medical College, Hangzhou, China

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