ArticleACS chemical neuroscience2014
PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia.The Journal of clinical investigation · 2019Trial
- Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors.ACS pharmacology & translational science · 2026Review
- Can Nuclear Imaging Detect Trained Immunity in Cardiovascular Disease?Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Preclinical validation of a novel brain-penetrant PET ligand for visualization of histone deacetylase 6: a potential imaging target for neurodegenerative diseases.European journal of nuclear medicine and molecular imaging · 2024Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.ACS medicinal chemistry letters · 2022Article
- Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [Pharmaceuticals (Basel, Switzerland) · 2022Article
- Development of a Novel, Small-Molecule Brain-Penetrant Histone Deacetylase Inhibitor That Enhances Spatial Memory Formation in Mice.Journal of medicinal chemistry · 2022Article
- Clinical validation of the novel HDAC6 radiotracer [European journal of nuclear medicine and molecular imaging · 2021Article
- Article
- In vivo human brain expression of histone deacetylases in bipolar disorder.Translational psychiatry · 2020Article
- Imaging HDACs In Vivo: Cross-Validation of the [Molecular imaging and biology · 2020Article
- Design, synthesis and biological evaluation of a series of CNS penetrant HDAC inhibitors structurally derived from amyloid-β probes.Scientific reports · 2019Article
- Neuroepigenetic signatures of age and sex in the living human brain.Nature communications · 2019Article
- HDAC2 dysregulation in the nucleus basalis of Meynert during the progression of Alzheimer's disease.Neuropathology and applied neurobiology · 2019Article
- Design, Synthesis, and Blood-Brain Barrier Transport Study of Pyrilamine Derivatives as Histone Deacetylase Inhibitors.ACS medicinal chemistry letters · 2018Article
- Fluid and imaging biomarkers for Alzheimer's disease: Where we stand and where to head to.Experimental gerontology · 2018Review
- Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2018Review
- Expression of HDAC2 but Not HDAC1 Transcript Is Reduced in Dorsolateral Prefrontal Cortex of Patients with Schizophrenia.ACS chemical neuroscience · 2017Article
- Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance.ACS chemical neuroscience · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Histone deacetylase (HDAC) enzymes have been demonstrated as critical components in maintaining chromatin homeostasis, CNS development, and normal brain function. Evidence in mouse models links HDAC expression to learning, memory, and mood-related behaviors; small molecule HDAC inhibitor tool compounds have been used to demonstrate the importance of specific HDAC subtypes in modulating CNS-disease-related behaviors in rodents. So far, no direct evidence exists to understand the quantitative changes in HDAC target engagement that are necessary to alter biochemistry and behavior in a living animal. Understanding the relationship between target engagement and in vivo effect is essential in refining new ways to alleviate disease. We describe here, using positron emission tomography (PET) imaging of rat brain, the in vivo target engagement of a subset of class I/IIb HDAC enzymes implicated in CNS-disease (HDAC subtypes 1, 2, 3, and 6). We found marked differences in the brain penetrance of tool compounds from the hydroxamate and benzamide HDAC inhibitor classes and resolved a novel, highly brain penetrant benzamide, CN147, chronic treatment with which resulted in an antidepressant-like effect in a rat behavioral test. Our work highlights a new translational path for understanding the molecular and behavioral consequences of HDAC target engagement.
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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.