MaltSci 麦伴科研

Appearance

Curated Papers > Recent high-impact research on "AI drug discovery" (IF ≥ 30, last 5 years)

m6A modification: recent advances, anticancer targeted drug discovery and beyond. ​

Literature Information ​

DOI10.1186/s12943-022-01510-2
PMID35164788
JournalMolecular cancer
Impact Factor33.9
JCR QuartileQ1
Publication Year2022
Times Cited193
KeywordsCancer, Chemosynthesis, Drug discovery, Modulators, Natural product
Literature TypeJournal Article, Research Support, Non-U.S. Gov't, Review
ISSN1476-4598
Pages52
Issue21(1)
AuthorsLi-Juan Deng, Wei-Qing Deng, Shu-Ran Fan, Min-Feng Chen, Ming Qi, Wen-Yu Lyu, Qi Qi, Amit K Tiwari, Jia-Xu Chen, Dong-Mei Zhang, Zhe-Sheng Chen

TL;DR ​

This review discusses the pivotal role of abnormal N6-methyladenosine (m6A) modification in cancer development and prognosis, highlighting its potential as a target for novel anticancer therapies. It emphasizes the integration of traditional medicine, modern drug discovery methods, and artificial intelligence in the development of m6A-targeted agents, showcasing a promising direction for future cancer treatment strategies.

Search for more papers on MaltSci.com ​

Cancer · Chemosynthesis · Drug discovery · Modulators · Natural product

Abstract ​

Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What specific roles do different m6A regulators play in cancer progression, and how can they be targeted for drug development?
  2. How do traditional medicine approaches compare to modern drug discovery platforms in the context of m6A-targeted therapies?
  3. What are the challenges and limitations of using artificial intelligence in the discovery of m6A-targeting anticancer drugs?
  4. Can you elaborate on the mechanisms through which m6A modification influences the efficacy of existing cancer treatments?
  5. What potential side effects or resistance mechanisms could arise from targeting m6A modifications in cancer therapy?

Key Findings ​

Research Background and Objectives ​

N6-methyladenosine (m6A) modification is a prevalent post-transcriptional modification in eukaryotic mRNAs, playing a critical role in various biological processes, including RNA stability, splicing, translation, and degradation. Aberrant m6A modifications are linked to the development and progression of several cancers, making m6A regulators promising targets for anticancer drug discovery. This review aims to summarize recent advances in understanding m6A modifications, explore the potential of m6A-targeted drugs derived from traditional medicines and modern synthetic methods, and highlight the role of artificial intelligence (AI) in drug discovery.

Main Methods/Materials/Experimental Design ​

The authors reviewed the literature on m6A modifications, focusing on the following key components:

  1. m6A Methylation Regulators:

    • Writers: METTL3, METTL14, WTAP
    • Erasers: FTO, ALKBH5
    • Readers: YTHDF1, YTHDF2, IGF2BPs

  2. Drug Discovery Approaches:

    • Traditional Medicine: Utilizing natural products from traditional medicine to discover m6A modulators.
    • Modern Drug Discovery: Implementing computer-aided drug design, including AI and chemosynthesis, to identify potential m6A-targeting compounds.

  3. Mechanisms of Action: The review outlines how m6A modification affects tumor progression by regulating oncogenes and tumor suppressor genes across various cancer types.

Mermaid diagram

Key Results and Findings ​

  • Role of m6A in Cancer: m6A regulators can act as either tumor promoters or suppressors, depending on the context and type of cancer. For example, METTL3 has been shown to promote proliferation in several cancers, while METTL14 often functions to inhibit tumor progression.
  • Natural Products: Various natural compounds (e.g., curcumin, resveratrol, quercetin) have demonstrated potential as m6A modulators, influencing cancer cell behavior by targeting m6A regulators.
  • AI in Drug Discovery: AI-based methods have accelerated the identification of small molecules that can selectively inhibit m6A demethylases like FTO, showcasing a novel approach to drug discovery.

Main Conclusions/Significance/Innovativeness ​

The review emphasizes the critical role of m6A modification in cancer biology and its potential as a therapeutic target. It advocates for integrating traditional medicine with modern drug discovery techniques, particularly AI, to enhance the efficiency and effectiveness of anticancer drug development. The authors highlight that while progress has been made, further exploration and validation of m6A modulators in clinical settings are necessary.

Research Limitations and Future Directions ​

  • Limitations: The review acknowledges that while many m6A regulators have been identified, only a few have been successfully targeted for drug development. Additionally, the clinical applicability of current m6A inhibitors remains to be fully validated.
  • Future Directions: The authors suggest that future research should focus on improving the specificity and efficacy of m6A-targeting agents, exploring the therapeutic potential of combining m6A modulation with existing cancer therapies, and further leveraging AI to streamline drug discovery processes.

References ​

  1. FTO-Dependent N 6-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. - Hao Huang;Yinu Wang;Manoj Kandpal;Guangyuan Zhao;Horacio Cardenas;Yanrong Ji;Anusha Chaparala;Edward J Tanner;Jianjun Chen;Ramana V Davuluri;Daniela Matei - Cancer research (2020)
  2. AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. - Yuko Ueda;Ikumi Ooshio;Yasuyuki Fusamae;Kaori Kitae;Megumi Kawaguchi;Kentaro Jingushi;Hiroaki Hase;Kazuo Harada;Kazumasa Hirata;Kazutake Tsujikawa - Scientific reports (2017)
  3. Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. - Jie Yu;Peiwei Chai;Minyue Xie;Shengfang Ge;Jing Ruan;Xianqun Fan;Renbing Jia - Genome biology (2021)
  4. Novel Small Molecule RNA m6A Demethylase AlkBH5 Inhibitors for Treating Cancer. - Ram W Sabnis - ACS medicinal chemistry letters (2021)
  5. m6A-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression. - Panpan Zhang;Qiuping He;Yuan Lei;Yingqin Li;Xin Wen;Mengzhi Hong;Jian Zhang;Xianyue Ren;Yaqin Wang;Xiaojing Yang;Qingmei He;Jun Ma;Na Liu - Cell death & disease (2018)
  6. Ythdc2 is an N6-methyladenosine binding protein that regulates mammalian spermatogenesis. - Phillip J Hsu;Yunfei Zhu;Honghui Ma;Yueshuai Guo;Xiaodan Shi;Yuanyuan Liu;Meijie Qi;Zhike Lu;Hailing Shi;Jianying Wang;Yiwei Cheng;Guanzheng Luo;Qing Dai;Mingxi Liu;Xuejiang Guo;Jiahao Sha;Bin Shen;Chuan He - Cell research (2017)
  7. The FTO/miR-181b-3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer. - Yuanyuan Xu;Shuang Ye;Nan Zhang;Shuhui Zheng;Huatao Liu;Kewen Zhou;Ling Wang;Yue Cao;Peng Sun;Tinghuai Wang - Cancer communications (London, England) (2020)
  8. m6 A RNA methylation: from mechanisms to therapeutic potential. - P Cody He;Chuan He - The EMBO journal (2021)
  9. DMDRMR-Mediated Regulation of m6A-Modified CDK4 by m6A Reader IGF2BP3 Drives ccRCC Progression. - Yinmin Gu;Shaoxi Niu;Yang Wang;Liqiang Duan;Yongbo Pan;Zhou Tong;Xu Zhang;Zhenyu Yang;Bo Peng;Xiaodong Wang;Xiaoqi Han;Yuxin Li;Tianyou Cheng;Yajuan Liu;Lina Shang;Tongfeng Liu;Xiwang Yang;Minxuan Sun;Siyuan Jiang;Chang Zhang;Ning Zhang;Qinong Ye;Shan Gao - Cancer research (2021)
  10. Chemical inhibitors make their RNA epigenetic mark. - Megan Cully - Nature reviews. Drug discovery (2019)

Literatures Citing This Work ​

  1. m6A Regulator-Mediated Methylation Modification Patterns and Characteristics in COVID-19 Patients. - Xin Qing;Qian Chen;Ke Wang - Frontiers in public health (2022)
  2. Construction of a Prognostic Model for KIRC and Identification of Drugs Sensitive to Therapies - A Comprehensive Biological Analysis Based on m6A-Related LncRNAs. - Dian Xia;Qi Liu;Songbai Yan;Liangkuan Bi - Frontiers in oncology (2022)
  3. Novel insights into the interaction between N6-methyladenosine methylation and noncoding RNAs in musculoskeletal disorders. - Juanjuan Han;Hui Kong;Xueqiang Wang;Xin-An Zhang - Cell proliferation (2022)
  4. Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance. - Hong Lin;Yuxi Wang;Pinghan Wang;Fangyi Long;Ting Wang - Molecular cancer (2022)
  5. Microarray and bioinformatic analysis reveal the parental genes of m6A modified circRNAs as novel prognostic signatures in colorectal cancer. - Wenken Liang;Liyuan Deng;Chune Mo;Wei Chen;Yu Sha;Jianling Shi;Xianliang Hou;Yuping Zhang;Min Yang;Minglin Ou - Frontiers in oncology (2022)
  6. Physio-pathological effects of N6-methyladenosine and its therapeutic implications in leukemia. - Wei-Wei Liu;Hao Wang;Xiao-Yu Zhu - Biomarker research (2022)
  7. A Novel hepatocellular carcinoma specific hypoxic related signature for predicting prognosis and therapeutic responses. - Guangzhen Cai;Jinghan Zhu;Deng Ning;Ganxun Li;Yuxin Zhang;Yixiao Xiong;Junnan Liang;Chengpeng Yu;Xiaoping Chen;Huifang Liang;Zeyang Ding - Frontiers in immunology (2022)
  8. Analysis of m6A-related signatures associated with the tumor immune microenvironment and predict survival in acute myeloid leukemia. - Shushu Yuan;Zhirong Cong;Jiali Ji;Li Zhu;Qi Jiang;Ying Zhou;Qian Shen;Daniela Damiani;Xiaohong Xu;Bingzong Li - Annals of translational medicine (2022)
  9. Implications of m6A methylation and microbiota interaction in non-small cell lung cancer: From basics to therapeutics. - Fen-Sheng Qiu;Jia-Qi He;Yu-Sen Zhong;Mei-Ying Guo;Chen-Huan Yu - Frontiers in cellular and infection microbiology (2022)
  10. Natural Products-Based Nanoformulations: A New Approach Targeting CSCs to Cancer Therapy. - Wenhao Liao;Yuchen Li;Jing Wang;Maoyuan Zhao;Nianzhi Chen;Qiao Zheng;Lina Wan;Yu Mou;Jianyuan Tang;Zhilei Wang - International journal of nanomedicine (2022)

... (183 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology