Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors

Abstract The role of LOXL2 in cancer has been widely demonstrated, but current therapies targeting LOXL2 are not yet fully developed. We believe that selective nature-derived inhibition of LOXL2 may provide a better therapeutic approach for the treatment of cancer. Therefore, we adopted a comprehens...

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Main Authors: Xiaowei Jia, Meng Liu, Yushi Tang, Jingyan Meng, Ruolin Fang, Xiting Wang, Cheng Li
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95530-9
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author Xiaowei Jia
Meng Liu
Yushi Tang
Jingyan Meng
Ruolin Fang
Xiting Wang
Cheng Li
author_facet Xiaowei Jia
Meng Liu
Yushi Tang
Jingyan Meng
Ruolin Fang
Xiting Wang
Cheng Li
author_sort Xiaowei Jia
collection DOAJ
description Abstract The role of LOXL2 in cancer has been widely demonstrated, but current therapies targeting LOXL2 are not yet fully developed. We believe that selective nature-derived inhibition of LOXL2 may provide a better therapeutic approach for the treatment of cancer. Therefore, we adopted a comprehensive approach combining deep learning and traditional computer-aided drug design methods to screen LOXL2 selective inhibitors. Bioactivity and affinity of the potential LOXL2 inhibitors were determined by molecular docking and virtual screening. At the same time, we experimentally tested the effect of potential LOXL2 inhibitors on cancer cells. Validation showed that it could inhibit proliferation and migration, promote apoptosis of CT26 cells, and reduce the expression level of LOXL2 protein. As a result, we identified a potent LOXL2 inhibitor: the natural product Forsythoside A, and demonstrated that Forsythoside A has an inhibitory effect on tumors.
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spelling doaj-art-68c3dbde83fb4f8b8c49c0b5b005ed452025-08-20T02:10:23ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-95530-9Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitorsXiaowei Jia0Meng Liu1Yushi Tang2Jingyan Meng3Ruolin Fang4Xiting Wang5Cheng Li6School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineSijiqing HospitalSchool of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineSchool of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineSchool of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineSchool of Traditional Chinese Medicine, Beijing University of Chinese MedicineSchool of Traditional Chinese Medicine, Tianjin University of Traditional Chinese MedicineAbstract The role of LOXL2 in cancer has been widely demonstrated, but current therapies targeting LOXL2 are not yet fully developed. We believe that selective nature-derived inhibition of LOXL2 may provide a better therapeutic approach for the treatment of cancer. Therefore, we adopted a comprehensive approach combining deep learning and traditional computer-aided drug design methods to screen LOXL2 selective inhibitors. Bioactivity and affinity of the potential LOXL2 inhibitors were determined by molecular docking and virtual screening. At the same time, we experimentally tested the effect of potential LOXL2 inhibitors on cancer cells. Validation showed that it could inhibit proliferation and migration, promote apoptosis of CT26 cells, and reduce the expression level of LOXL2 protein. As a result, we identified a potent LOXL2 inhibitor: the natural product Forsythoside A, and demonstrated that Forsythoside A has an inhibitory effect on tumors.https://doi.org/10.1038/s41598-025-95530-9LOXL2CancerDeep learningDrug discovery
spellingShingle Xiaowei Jia
Meng Liu
Yushi Tang
Jingyan Meng
Ruolin Fang
Xiting Wang
Cheng Li
Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
Scientific Reports
LOXL2
Cancer
Deep learning
Drug discovery
title Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
title_full Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
title_fullStr Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
title_full_unstemmed Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
title_short Artificial intelligence accelerates the identification of nature-derived potent LOXL2 inhibitors
title_sort artificial intelligence accelerates the identification of nature derived potent loxl2 inhibitors
topic LOXL2
Cancer
Deep learning
Drug discovery
url https://doi.org/10.1038/s41598-025-95530-9
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