Trial reportCancer discovery2023
MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.
Trial report in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
134 citing papers in PubMed, 172 citations in OpenAlex.
- Article
- Protein arginine methyltransferases as metabolic regulators: many roles beyond cancer.Science China. Life sciences · 2026Review
- Patient-Derived Organoid Models and Precision HIPEC in Diffuse Malignant Peritoneal Mesothelioma: Modeling Heterogeneity to Address Recurrence.International journal of molecular sciences · 2026Review
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- TNG961 Is a Selective Oral HBS1L Molecular Glue Degrader for the Treatment of FOCAD-Deleted Cancers.Cancer discovery · 2026Article
- Review
- Acquired Resistance to the PRMT5 Inhibitor Confers Collateral Sensitivity to MEK Inhibition inBiomolecules · 2026Article
- Microtubule disruption and apoptotic induction by Vibrio cholerae haemagglutinin protease: Implications for anticancer therapy in colon and gastric tumours.The Indian journal of medical research · 2026Article
- Genetic analysis of primary lung interdigitating dendritic cell sarcomas.The Journal of pathology · 2026Article
- MTAP Deficiency as a Metabolic Vulnerability in Cancer: Implications for Synthetic Lethal Therapy.Cancer science · 2026Review
- Temporal control of sgRNA library activation unlocks large-scale in vivo CRISPR screens.Cell reports methods · 2026Article
- Quantitative Global Proteomics of Formalin-Fixed Paraffin-Embedded Tumors Identifies Dimethylated G3BP1 at Arginine 460 as a Robust Pharmacodynamic Biomarker of Methylthioadenosine Phosphorylase-Selective Protein Arginine Methyltransferase 5 Inhibition.Journal of proteome research · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Coupled-enzyme assay for MTAP activity in biological samples.Analytical biochemistry · 2026Article
- Targeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer.Histology and histopathology · 2026Article
- An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.EBioMedicine · 2026Article
- Arginine Methylation in Alternative Splicing: Implications for Cancer Therapy.Journal of cellular physiology · 2026Review
- Pancreatic Cancer: Translating Tumor Biology into Actionability.Cancer discovery · 2026Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 1 country.
Funding
Abstract
Previous studies implicated protein arginine methyltransferase 5 (PRMT5) as a synthetic lethal target for MTAP-deleted (MTAP del) cancers; however, the pharmacologic characterization of small-molecule inhibitors that recapitulate the synthetic lethal phenotype has not been described. MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent activity and cell viability with >70-fold selecti-vity in HCT116 MTAP del compared with HCT116 MTAP wild-type (WT) cells. MRTX1719 demonstrated dose-dependent antitumor activity and inhibition of PRMT5-dependent SDMA modification in MTAP del tumors. In contrast, MRTX1719 demonstrated minimal effects on SDMA and viability in MTAP WT tumor xenografts or hematopoietic cells. MRTX1719 demonstrated marked antitumor activity across a panel of xenograft models at well-tolerated doses. Early signs of clinical activity were observed including objective responses in patients with MTAP del melanoma, gallbladder adenocarcinoma, mesothelioma, non-small cell lung cancer, and malignant peripheral nerve sheath tumors from the phase I/II study. SIGNIFICANCE: PRMT5 was identified as a synthetic lethal target for MTAP del cancers; however, previous PRMT5 inhibitors do not selectively target this genotype. The differentiated binding mode of MRTX1719 leverages the elevated MTA in MTAP del cancers and represents a promising therapy for the ∼10% of patients with cancer with this biomarker. See related commentary by Mulvaney, p. 2310. This article is featured in Selected Articles from This Issue, p. 2293.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.