ArticleJournal of medicinal chemistry2014
Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
65 citing papers in PubMed, 115 citations in OpenAlex.
- KMT5A-mediated methylation of IRF3 promotes tumor progression through immune suppression.iScience · 2026Article
- SETD8-mediated mono-methylation of YAP at K76 promotes K48-linked polyubiquitination and degradation to suppress colorectal cancer.Cell death and differentiation · 2026Article
- Development of High-Affinity CHD1 Chromodomain Inhibitors.Journal of medicinal chemistry · 2026Article
- SETD8 promotes ovarian clear cell carcinoma by epigenetically activating RNA metabolism genes via H4K20me1.Scientific reports · 2026Article
- The lysine methyltransferase KMT5a and p53 regulate the expression of the key autophagy adaptor p62/SQSTM1 in glioblastoma.Cell communication and signaling : CCS · 2026Article
- Discovery of a Potent, Selective, and In Vivo Efficacious Covalent Inhibitor for Lysine Methyltransferase SETD8.Journal of medicinal chemistry · 2026Article
- Impact of SETD8/KMT5A overexpression on hepatocellular carcinoma progression and prognosis.PloS one · 2026Article
- The H4K20-mono-methyltransferase SETD8 promotes global accessibility of infecting herpes simplex virus genomes.Journal of virology · 2025Article
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Multiple functions of the lysine methyltransferase KMT5a in cancer: potential targets for innovative therapies.Clinical epigenetics · 2025Review
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- Genome editing or small molecule inhibition of KMT5A in CAR-T cells enhances antitumor immunity.Journal for immunotherapy of cancer · 2025Article
- Epigenetic editing and epi-drugs: a combination strategy to simultaneously target KDM4 as a novel anticancer approach.Clinical epigenetics · 2025Article
- SUMOylation of SETD8 Promotes Tumor Growth by Methylating and Stabilizing MYC in Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- C1QMolecular cancer · 2025Article
- SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.Cell death & disease · 2025Article
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- SETD8 inhibition targets cancer cells with increased rates of ribosome biogenesis.Cell death & disease · 2024Article
- Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer.Oncology reports · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
The lysine methyltransferase SETD8 is the only known methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20). Monomethylation of H4K20 has been implicated in regulating diverse biological processes including the DNA damage response. In addition to H4K20, SETD8 monomethylates non-histone substrates including proliferating cell nuclear antigen (PCNA) and promotes carcinogenesis by deregulating PCNA expression. However, selective inhibitors of SETD8 are scarce. The only known selective inhibitor of SETD8 to date is nahuoic acid A, a marine natural product, which is competitive with the cofactor. Here, we report the discovery of the first substrate-competitive inhibitor of SETD8, UNC0379 (1). This small-molecule inhibitor is active in multiple biochemical assays. Its affinity to SETD8 was confirmed by ITC (isothermal titration calorimetry) and SPR (surface plasmon resonance) studies. Importantly, compound 1 is selective for SETD8 over 15 other methyltransferases. We also describe structure-activity relationships (SAR) of this series.
Indexed as
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.