{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302574/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302574"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological inhibition of METTL1 as a therapy against solid and haematological cancers [Ribo-Seq]","description":"The N7-methylguanosine (m7G) modification is one of the most prevalent modifications on tRNA, mainly catalysed by the METTL1-WDR4 protein complex. The m7G methyltranferase 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 cellular 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":"2026/08/12"},"accession":"GSE302574","cross_references":{"GSM":["GSM9106413","GSM9106412","GSM9106411","GSM9106410","GSM9106409","GSM9106408","GSM9106407","GSM9106406","GSM9106405","GSM9106404","GSM9106414","GSM9106403"],"GPL":["34284"],"GSE":["302574"],"taxon":["Homo sapiens"]}}