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. 2024 Aug 6;15(9):1491-1499.
doi: 10.1021/acsmedchemlett.4c00216. eCollection 2024 Sep 12.

Virtual Screening and Molecular Docking: Discovering Novel METTL3 Inhibitors

Junyi Yang  1   2 , Yanwen He  1   2 , Youkun Kang  1   2 , Liteng Shen  3 , Wen Zhang  1   2 , Yumeng Yan  1   2 , Xinyi Li  1   2 , Wenhai Huang  1   2 , Xiangwei Xu  1   2
Affiliations

Virtual Screening and Molecular Docking: Discovering Novel METTL3 Inhibitors

Junyi Yang et al. ACS Med Chem Lett. .

Abstract

Methyltransferase-like 3 (METTL3) is an RNA methyltransferase that catalyzes the N6 -methyladenosine (m6A) modification of mRNA in eukaryotic cells. Past studies have shown that METTL3 is highly expressed in various cancers and is closely related to tumor development. Therefore, METTL3 inhibitors have received widespread attention as effective treatments for different types of tumors. This study proposes a hybrid high-throughput virtual screening (HTVS) protocol that combines structure-based methods with geometric deep learning-based DeepDock algorithms. We identified unique skeleton inhibitors of METTL3 from our self-built internal database. Among them, compound C3 showed significant inhibitory activity on METTL3, and further molecular dynamics simulations were performed to provide more details about the binding conformation. Overall, our research demonstrates the effectiveness of hybrid virtual algorithms, which is of great significance for understanding the biological functions of METTL3 and developing treatment methods for related diseases.

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Conflict of interest statement

The authors declare no competing financial interest.

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