ArticleBiochemical pharmacology2016
The histone acetyltransferase p300 inhibitor C646 reduces pro-inflammatory gene expression and inhibits histone deacetylases.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- TDP-43 Acetylation at the Neuroimmune Interface: A Hypothesis-Driven Framework for Peripheral Inflammatory Stratotypes in ALS.Neurochemical research · 2026Review
- P300 in Inflammation: An Updated Perspective on Its Molecular Mechanisms and Therapeutic Potential.Inflammation · 2026Review
- P300-mediated H3K18 acetylation triggers necroptosis via modulation of KRT18 transcription in diabetic nephropathy.Acta biochimica et biophysica Sinica · 2026Article
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review).Oncology reports · 2026Review
- Protein acylation in inflammatory diseases: from mechanisms to therapeutic strategies.Cell communication and signaling : CCS · 2025Review
- Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.JACS Au · 2025Article
- Development of C646-Based Proteolysis Targeting Chimeras Degraders of the Lysine Acetyltransferases CBP and p300.ChemMedChem · 2025Article
- Epigenetic dynamics in meniscus cell migration and its zonal dependency in response to inflammatory conditions.APL bioengineering · 2025Article
- Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4 Pathway via the p300-p53 Axis.Biomolecules & therapeutics · 2025Article
- Epigenetic regulation espeically histone modifications in breast cancer: A viable and emerging targeted therapeutic strategy.Journal of Cancer · 2025Review
- Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials.Clinical and translational medicine · 2024Review
- Epigenetic Dynamics in Meniscus Cell Migration and its Zonal Dependency in Response to Inflammatory Conditions: Implications for Regeneration Strategies.bioRxiv : the preprint server for biology · 2024Article
- Histone acetyltransferases and external demands influence task switching inBiology letters · 2023Article
- First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8.Journal of medicinal chemistry · 2023Article
- TRPM3-Induced Gene Transcription Is under Epigenetic Control.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Identifying Small-Molecule Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase by Establishing a Fluorometric Assay.Frontiers in immunology · 2022Article
- A Src-H3 acetylation signaling axis integrates macrophage mechanosensation with inflammatory response.Biomaterials · 2021Article
- Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp12/7/8 RNA-dependent RNA polymerase.The Biochemical journal · 2021Article
- Role of Epigenetics in the Regulation of Immune Functions of the Skin.The Journal of investigative dermatology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Lysine acetylations are reversible posttranslational modifications of histone and non-histone proteins that play important regulatory roles in signal transduction cascades and gene expression. Lysine acetylations are regulated by histone acetyltransferases as writers and histone deacetylases as erasers. Because of their role in signal transduction cascades, these enzymes are important players in inflammation. Therefore, histone acetyltransferase inhibitors could reduce inflammatory responses. Among the few histone acetyltransferase inhibitors described, C646 is one of the most potent (Ki of 0.4μM for histone acetyltransferase p300). C646 was described to affect the NF-κB pathway; an important pathway in inflammatory responses, which is regulated by acetylation. This pathway has been implicated in asthma and COPD. Therefore, we hypothesized that via regulation of the NF-κB signaling pathway, C646 can inhibit pro-inflammatory gene expression, and have potential for the treatment of inflammatory lung diseases. In line with this, we demonstrate here that C646 reduces pro-inflammatory gene expression in RAW264.7 murine macrophages and murine precision-cut lung slices. To unravel its effects on cellular substrates we applied mass spectrometry and found, counterintuitively, a slight increase in acetylation of histone H3. Based on this finding, and structural features of C646, we presumed inhibitory activity of C646 on histone deacetylases, and indeed found inhibition of histone deacetylases from 7μM and higher concentrations. This indicates that C646 has potential for further development towards applications in the treatment of inflammation, however, its newly discovered lack of selectivity at higher concentrations needs to be taken into account.
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