ArticleACS medicinal chemistry letters2019
Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Methionine restriction for cancer therapy: From preclinical studies to clinical trials.Cancer pathogenesis and therapy · 2026Review
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- Chemotype- and Target-Driven Genome Mining for a New Natural Product Inhibitor of Bacterial Peptide Deformylase.Journal of the American Chemical Society · 2025Article
- In silico protein structural analysis of PRMT5 and RUVBL1 mutations arising in human cancers.Cancer genetics · 2025Article
- A review of the known MTA-cooperative PRMT5 inhibitors.RSC advances · 2024Review
- Resistance to PRMT5-targeted therapy in mantle cell lymphoma.Blood advances · 2024Article
- PRMT5 triggers glucocorticoid-induced cell migration in triple-negative breast cancer.Life science alliance · 2023Article
- Chemical probes and methods for the study of protein arginine methylation.RSC chemical biology · 2023Review
- Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation.Nature communications · 2023Article
- Design, Synthesis and Biological Evaluation of Novel and Potent Protein Arginine Methyltransferases 5 Inhibitors for Cancer Therapy.Molecules (Basel, Switzerland) · 2022Article
- Cryo-EM structure-based selection of computed ligand poses enables design of MTA-synergic PRMT5 inhibitors of better potency.Communications biology · 2022Article
- The Structural Effects of Phosphorylation of Protein Arginine Methyltransferase 5 on Its Binding to Histone H4.International journal of molecular sciences · 2022Article
- High-resolution structures of the SARS-CoV-2 N7-methyltransferase inform therapeutic development.Nature structural & molecular biology · 2022Article
- Exploring Methods of Targeting Histone Methyltransferases and Their Applications in Cancer Therapeutics.ACS chemical biology · 2022Review
- High resolution structures of the SARS-CoV-2 N7-methyltransferase inform therapeutic development.Research square · 2022Article
- Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity.Molecular cancer therapeutics · 2021Article
- PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.Cancers · 2021Review
- Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cancer synthetic vulnerabilities to protein arginine methyltransferase inhibitors.Current opinion in pharmacology · 2021Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein arginine methyltransferase 5 (PRMT5) is known to symmetrically dimethylate numerous cytosolic and nuclear proteins that are involved in a variety of cellular processes. Recent findings have revealed its potential as a cancer therapeutic target. PRMT5 possesses a cysteine (C449) in the active site, unique to PRMT5. Therefore, covalent PRMT5 inhibition is an attractive chemical approach. Herein, we report an exciting discovery of a series of novel hemiaminals that under physiological conditions can be converted to aldehydes and react with C449 to form covalent adducts, which presumably undergo an unprecedented elimination to form the thiol-vinyl ethers, as indicated by electron density in the co-crystal structure of the PRMT5/MEP50 complex.
Identifiers
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Registered trials
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.