Small molecule inhibitors targeting m6A regulators

J Hematol Oncol. 2024 May 6;17(1):30. doi: 10.1186/s13045-024-01546-5.


As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure-activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.

Keywords: Cancer therapy; Drug targets; Mechanism; N6-methyladenosine; Small molecule modulators.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine* / analogs & derivatives
  • Adenosine* / metabolism
  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Epigenesis, Genetic / drug effects
  • Humans
  • Neoplasms* / drug therapy
  • Small Molecule Libraries* / pharmacology
  • Small Molecule Libraries* / therapeutic use


  • Adenosine
  • Antineoplastic Agents
  • N-methyladenosine
  • Small Molecule Libraries