ArticleACS medicinal chemistry letters2020
Allosteric Modulation of Protein Arginine Methyltransferase 5 (PRMT5).
Article in ACS medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Negative allosteric regulation of protein arginine methyltransferase 1 (PRMT1) through half-of-sites reactivity.The Journal of biological chemistry · 2026Article
- Protein arginine methyltransferases as regulators of phase separation: implications in cancer and neurodegenerative diseases.European biophysics journal : EBJ · 2026Review
- Exploring the Structural Basis of Cryptic Pocket Formation Driven by Extensive Protein Conformational Changes in Drug Targets.Journal of chemical theory and computation · 2026Article
- A BRET biosensor for measuring uncompetitive engagement of PRMT5 complexes in cells.Nature communications · 2025Article
- Discovery of a Potent and Selective Protein Arginine Methyltransferase 5 (PRMT5) PROTAC Degrader.Journal of medicinal chemistry · 2025Article
- A review of the known MTA-cooperative PRMT5 inhibitors.RSC advances · 2024Review
- Review
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- 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
- Novel Chemicals Derived from Tadalafil Exhibit PRMT5 Inhibition and Promising Activities against Breast Cancer.International journal of molecular sciences · 2022Article
- Recent applications of computational methods to allosteric drug discovery.Frontiers in molecular biosciences · 2022Review
- 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
- Protein arginine methylation: from enigmatic functions to therapeutic targeting.Nature reviews. Drug discovery · 2021Review
- A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes.Biomolecules · 2021Article
- A First-in-Class, Highly Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 6.Journal of medicinal chemistry · 2021Article
- Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein arginine methyltransferase 5 (PRMT5) belongs to a family of enzymes that regulate the posttranslational modification of histones and other proteins via methylation of arginine. Methylation of histones is linked to an increase in transcription and regulates a manifold of functions such as signal transduction and transcriptional regulation. PRMT5 has been shown to be upregulated in the tumor environment of several cancer types, and the inhibition of PRMT5 activity was identified as a potential way to reduce tumor growth. Previously, four different modes of PRMT5 inhibition were known-competing (covalently or non-covalently) with the essential cofactor S-adenosyl methionine (SAM), blocking the substrate binding pocket, or blocking both simultaneously. Herein we describe an unprecedented conformation of PRMT5 in which the formation of an allosteric binding pocket abrogates the enzyme's canonical binding site and present the discovery of potent small molecule allosteric PRMT5 inhibitors.
Identifiers
What OpenQuestion holds
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.