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