{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303386/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"," Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303386"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological inhibition of METTL1 as a novel anti-cancer strategy","description":"The N7-methylguanosine (m7G) modification is one of the most prevalent modifications on tRNA, mainly catalysed by the METTL1-WDR4 protein complex1-4. The m7G methyltransferase METTL1 has been connected to oncogenic transformation and maintenance of several aggressive malignancies but the impact of a therapeutic targeting a tRNA-modifying enzyme is yet to be determined. Here, we present the development and characterisation of STM9005, a highly selective and potent first-in-class tRNA methyltransferase inhibitor of METTL1. Treatment of numerous tumour models with STM9005 reduces cancer growth, causes differentiation changes and dysregulates cell cycle progression. These cellular effects were accompanied by a selective decrease of m7G on a subset of tRNAs and a reduction in their expression levels, which led to an impact on oncogenic mRNA translation. We illustrate that pharmacological inhibition of METTL1 in vivo impairs tumour growth and leads to a significant prolongation of survival in various mouse cancer models of different tissue origin. Collectively, our results provide strong proof-of-concept that targeting of tRNA methylation is a novel avenue of anti-cancer therapy, and illustrate that catalytic inhibition of METTL1 represents a novel therapeutic strategy against a number of aggressive malignancies.","dates":{"publication":"2026/08/17"},"accession":"GSE303386","cross_references":{"GSM":["GSM9125010","GSM9125002","GSM9125013","GSM9125003","GSM9125014","GSM9125000","GSM9125011","GSM9125012","GSM9125001","GSM9125006","GSM9125007","GSM9125015","GSM9125004","GSM9125005","GSM9125016","GSM9124999","GSM9125008","GSM9124997","GSM9124998","GSM9125009"],"GPL":["34284","34290"],"GSE":["303386"],"taxon":["Mus musculus"," Homo sapiens"]}}