A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO

Lai, Gan-Qiang; Li, Yali; Zhu, Heping; Zhang, Tao; Gao, Jing; Zhou, Hu; Yang, Cai-Guang

doi:10.1039/d3cb00230f

RSC Chem. Biol.

2024

DOI: 10.1039/d3cb00230f

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A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO

Gan-Qiang Lai,

Yali Li,

Heping Zhu

et al.

Abstract: We discovered that TD19 covalently and selectively inhibits ALKBH5 rather than FTO demethylase in both protein-based and tumor cell-based assays.

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Cited by 8 publications

References 49 publications

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RNA modification in normal hematopoiesis and hematologic malignancies

Chen,

Yuan,

Zhou

et al. 2024

MedComm

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N6‐methyladenosine (m6A) is the most abundant RNA modification in eukaryotic cells. Previous studies have shown that m6A plays a critical role under both normal physiological and pathological conditions. Hematopoiesis and differentiation are highly regulated processes, and recent studies on m6A mRNA methylation have revealed how this modification controls cell fate in both normal and malignant hematopoietic states. However, despite these insights, a comprehensive understanding of its complex roles between normal hematopoietic development and malignant hematopoietic diseases remains elusive. This review first provides an overview of the components and biological functions of m6A modification regulators. Additionally, it highlights the origin, differentiation process, biological characteristics, and regulatory mechanisms of hematopoietic stem cells, as well as the features, immune properties, and self‐renewal pathways of leukemia stem cells. Last, the article systematically reviews the latest research advancements on the roles and mechanisms of m6A regulatory factors in normal hematopoiesis and related malignant diseases. More importantly, this review explores how targeting m6A regulators and various signaling pathways could effectively intervene in the development of leukemia, providing new insights and potential therapeutic targets. Targeting m6A modification may hold promise for achieving more precise and effective leukemia treatments.

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RNA modification in normal hematopoiesis and hematologic malignancies

Chen,

Yuan,

Zhou

et al. 2024

MedComm

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Discovery of a potent PROTAC degrader for RNA demethylase FTO as antileukemic therapy

Liu,

Qiu,

Suo

et al. 2024

Acta Pharmaceutica Sinica B

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Small molecules that regulate the N6-methyladenosine RNA modification as potential anti-cancer agents

Harrahill,

Hadden

2024

European Journal of Medicinal Chemistry

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A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO

Abstract: We discovered that TD19 covalently and selectively inhibits ALKBH5 rather than FTO demethylase in both protein-based and tumor cell-based assays.

Cited by 8 publications

References 49 publications

RNA modification in normal hematopoiesis and hematologic malignancies

RNA modification in normal hematopoiesis and hematologic malignancies

Discovery of a potent PROTAC degrader for RNA demethylase FTO as antileukemic therapy

Small molecules that regulate the N6-methyladenosine RNA modification as potential anti-cancer agents

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