Discovery of Novel MRNA Demethylase FTO Inhibitors Against Esophageal cancer

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Jul 14

PMID 35833378

Authors

Bo Qin

Qian Bai

Dan Yan

Fanxiang Yin

Zhu Zhu

Chaoyuan Xia

Yang Yang

Yi Zhao

Affiliations

Soon will be listed here.

Abstract

A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound exhibited the most robust inhibition of FTO with an IC value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.

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