A novel inhibitor of N ⁶-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities.

ABSTRACT: N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m

SUBMITTER: Xie G 

PROVIDER: S-EPMC8897214 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature