Issue 5, 2021

Targeting the RNA demethylase FTO for cancer therapy

Abstract

N 6-Methyladenosine (m6A) is the most prevalent internal modification on mRNA and represents a new layer of gene expression in eukaryotes. The field of m6A-encoded epitranscriptomics was rejuvenated with the discovery of fat mass and obesity-associated protein (FTO) as the first m6A demethylase responsible for RNA modification in cells. Increasing evidence has revealed that FTO is significantly involved in physiological processes, and its dysregulation is implicated in various human diseases. Considering this functional significance, developing small-molecule modulators of the FTO protein represents a novel direction for biology research. However, such modulators remain in the early stages of development. Here, our review mainly focuses on the progress of FTO inhibitor development to date. We summarize screening methods used to identify FTO modulators, techniques used to assess the biological effects of these modulators, strategies used to achieve selective inhibition of FTO rather than its homologues, and the results of investigations of FTO modulator modes of action and anticancer efficacy. Thus, this review aims to facilitate novel chemical entity discovery, probe FTO biology, and promote the validation of FTO as a clinical drug target for cancer treatment.

Graphical abstract: Targeting the RNA demethylase FTO for cancer therapy

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Article information

Article type
Review Article
Submitted
05 4 2021
Accepted
26 7 2021
First published
26 7 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 1352-1369

Targeting the RNA demethylase FTO for cancer therapy

L. Zhou, H. Xu, Y. Huang and C. Yang, RSC Chem. Biol., 2021, 2, 1352 DOI: 10.1039/D1CB00075F

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