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    Home > Medical News > Medical World News > New tumor target METTL3, potential first-in-class leukemia new drug appears

    New tumor target METTL3, potential first-in-class leukemia new drug appears

    • Last Update: 2021-05-10
    • Source: Internet
    • Author: User
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    Text | Bailu

    Scientists have taken another landmark step in the development of new drugs for acute myeloid leukemia (AML).


    On April 26, researchers from the University of Cambridge published a study in the journal Nature, reporting a new treatment for AML.


    Source: Nature

    Source: Nature

    Professor Tony Kouzarides, who led the research, said: “Protein plays a vital role in our body functions.


    METTL3 target global research status (data source: NextPharma)

    METTL3 target global research status (data source: NextPharma)

    There are more than 170 modifications in RNA, of which N6-methyladenine (m6A) methylation is one of the most common epigenetic modifications on RNA molecules.


    Schematic diagram of the domain of METTL3 (Source: Journal of Hematology & Oncology)

    Schematic diagram of the domain of METTL3 (Source: Journal of Hematology & Oncology)

    In fact, as early as 2017, a team led by Professor Kouzardides published a study in the journal Nature, pointing out that the METTL3 enzyme plays a key role in the development and maintenance of AML, and identified this enzyme as a potential therapeutic target for AML.


    Source: Nature

    Source: Nature

    Now, Professor Kouzardides and his colleagues have discovered a drug-like small molecule STM2457 that can inhibit METL3.


    Source: Nature

    Source: Nature

    Specifically, in order to study the anti-leukemia potential of STM2457, the researchers tested the molecule on cell lines from AML patients and found that it significantly reduced the growth and proliferation of these cells in a concentration-dependent manner (Figure a below).


    Source: Nature

    Source: Nature

    After obtaining positive evidence in in vitro experiments, the researchers transplanted cells from AML patients into immunocompromised mice to establish a disease model and treated the mice with STM2457.


    In vivo studies have shown that STM2457 can prevent the expansion of AML and reduce key leukemia stem cells (Source: Nature)

    In vivo studies have shown that STM2457 can prevent the expansion of AML and reduce key leukemia stem cells (Source: Nature)

    Collectively, these results reveal that METL3 inhibition can be used as a potential therapeutic strategy for anti-AML, and provide a proof of concept for targeting RNA-modifying enzymes as a promising new approach to anti-cancer therapy.


    "This is a brand-new area of ​​cancer research.


    Reference materials:

    Reference materials:

    1# Eliza Yankova et al.


    1# Eliza Yankova et al.


    2# Isaia Barbieri et al.


    3# Scientists develop new class of cancer drug with potential to treat leukaemia (Source: University of Cambridge official website)

    4# Chengwu Zeng et al.


    4# Chengwu Zeng et al.


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