# The METTL3 inhibitor STM2457 suppresses gastric cancer progression by modulating m6A RNA modification

## TL;DR

A new drug called STM2457 inhibits a protein called METTL3, which slows the growth of gastric cancer cells in lab and animal studies.

## Contribution

STM2457 is identified as a METTL3 inhibitor with therapeutic potential for gastric cancer through m6A RNA modification modulation.

## Key findings

- STM2457 suppresses gastric cancer cell proliferation and migration by inhibiting METTL3.
- The drug promotes apoptosis and arrests the cell cycle in the S phase in gastric cancer cells.
- STM2457 inhibits tumor growth in a mouse xenotransplantation model.

## Abstract

Gastric cancer (GC) is one of the most common and lethal cancers globally. methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA methylation plays a crucial role in tumor initiation and progression by regulating RNA function. STM2457, a highly efficient METTL3 inhibitor, can inhibit METTL3 activity and may serve as a potential therapeutic strategy in cancers. However, the role of STM2457 for GC cells is still unknown. In this study, we analyzed the expression profile data of GC in TCGA and GEO databases, and further explored the expression involvement of METTL3 in GC cell line, investigated the therapeutic effect of STM2457 targeted inhibition of METTL3 in GC both in vitro and in vivo experiments. The results indicated that STM2457 could suppress GC cell proliferation and migration by inhibiting METTL3, and also promoted cell apoptosis and arrest the cell cycle in S phase. In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.