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Mining for METTL3 inhibitors to suppress cancer

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The RNA methyltransferase METTL3 catalyzes N6-methyladenosine (m6A) modification of messenger RNAs (mRNAs). It is overexpressed in many types of cancer, including acute myelogenous leukemia (AML), and promotes cancer cell growth and tumorigenicity. Now, a selective small molecule inhibitor of METTL3 shows significant antileukemic effects in preclinical AML models, highlighting the promise of pharmacological METTL3 inhibition as a new cancer therapy.

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Fig. 1: METTL3 inhibition is a promising therapy against AML.

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Acknowledgements

R.I.G. is supported by an Outstanding Investigator Award (R35CA232115) and R01 grant (R01CA233671) from the National Cancer Institute (NCI) of the NIH.

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Authors and Affiliations

  1. Stem Cell Program, Division of Hematology/Oncology, Boston Children’s Hospital, Boston, MA, USA

    Jiazhi Li & Richard I. Gregory

  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Jiazhi Li & Richard I. Gregory

  3. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Richard I. Gregory

  4. Harvard Stem Cell Institute, Cambridge, MA, USA

    Richard I. Gregory

  5. Harvard Initiative for RNA Medicine, Boston, MA, USA

    Richard I. Gregory

Authors
  1. Jiazhi Li
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  2. Richard I. Gregory
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J.L. and R.I.G. wrote the manuscript.

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Correspondence to Richard I. Gregory.

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Competing interests

R.I.G. is a cofounder and scientific advisory board member of 28-7 Therapeutics and Theon Therapeutics.

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Li, J., Gregory, R.I. Mining for METTL3 inhibitors to suppress cancer. Nat Struct Mol Biol 28, 460–462 (2021). https://doi.org/10.1038/s41594-021-00606-5

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