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ORIGINAL RESEARCH article

Front. Chem.
Sec. Theoretical and Computational Chemistry
Volume 12 - 2024 | doi: 10.3389/fchem.2024.1482758
This article is part of the Research Topic Dynamics and Functional Exploration of Pharmacologically Active Proteins View all articles

Screening, Optimization, and ADMET Evaluation of HCJ007 for Pancreatic Cancer Treatment Through Active Learning and Dynamics Simulation

Provisionally accepted
Yunyun Xu Yunyun Xu 1,2Qiang Wang Qiang Wang 3GaoQiang Xu GaoQiang Xu 3YouJian Xu YouJian Xu 3yiping mou yiping mou 1,2*
  • 1 Hangzhou Medical College, Hangzhou, China
  • 2 Zhejiang Provincial People's Hospital, hangzhou， Zhejiang province, China
  • 3 Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang Province, China

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

    In this study, we leveraged a sophisticated active learning model to enhance virtual screening for SQLE inhibitors. The model's improved predictive accuracy identified compounds with significant advantages in binding affinity and thermodynamic stability. Detailed analyses, including molecular dynamics simulations and ADMET profiling, were conducted, particularly focusing on compounds CMNPD11566 and its derivative HCJ007. CMNPD11566 showed stable interactions with SQLE, while HCJ007 exhibited improved binding stability and more frequent interactions with key residues, indicating enhanced dynamic adaptability and overall binding effectiveness. ADMET data comparison highlighted HCJ007's superior profile in terms of lower toxicity and better drug-likeness. Our findings suggest HCJ007 as a promising candidate for SQLE inhibition, with significant improvements over CMNPD11566 in various pharmacokinetic and safety parameters. The study underscores the efficacy of computational models in drug discovery and the importance of comprehensive preclinical evaluations.

    Keywords: Marine Natural Products, Screening of SQLE Inhibitors, Active Learning Model, ADMET analysis, molecular dynamics simulations, Molecular modification

    Received: 18 Aug 2024; Accepted: 12 Nov 2024.

    Copyright: © 2024 Xu, Wang, Xu, Xu and mou. 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: yiping mou, Hangzhou Medical College, Hangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.