ArticleACS chemical neuroscience2014
Image-guided synthesis reveals potent blood-brain barrier permeable histone deacetylase inhibitors.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Selective histone deacetylase inhibition as a therapeutically relevant strategy in H3K27M-glioma.Neuro-oncology · 2026Article
- Epigenetic Control of Stress-Induced Depression: Emerging Roles of HDAC3 and HDAC6.International journal of molecular sciences · 2026Review
- Biosynthesized nanoparticles of Tibetan medicine mercuric sulfide preparation to promote endocytosis and realize drug crossing through blood brain barrier.Journal of nanobiotechnology · 2025Article
- Pretargeted imaging beyond the blood-brain barrier.RSC medicinal chemistry · 2023Article
- Microliter-scale reaction arrays for economical high-throughput experimentation in radiochemistry.Scientific reports · 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
- The role of altered protein acetylation in neurodegenerative disease.Frontiers in aging neuroscience · 2022Review
- Comprehensive Analysis of the Differential Expression and Prognostic Value of Histone Deacetylases in Glioma.Frontiers in cell and developmental biology · 2022Article
- Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.Neuromolecular medicine · 2021Review
- A Baboon Brain Atlas for Magnetic Resonance Imaging and Positron Emission Tomography Image Analysis.Frontiers in neuroanatomy · 2021Article
- Combination Treatment of CI-994 With Etoposide Potentiates Anticancer Effects Through a Topoisomerase II-Dependent Mechanism in Atypical Teratoid/Rhabdoid Tumor (AT/RT).Frontiers in oncology · 2021Article
- Molecular imaging of Alzheimer's disease-related gamma-secretase in mice and nonhuman primates.The Journal of experimental medicine · 2020Article
- Article
- A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging.Molecules (Basel, Switzerland) · 2020Article
- The Neuroprotective Effect of the HDAC2/3 Inhibitor MI192 on the Penumbra After Photothrombotic Stroke in the Mouse Brain.Molecular neurobiology · 2020Article
- Rapidly (and Successfully) Translating Novel Brain Radiotracers From Animal Research Into Clinical Use.Frontiers in neuroscience · 2020Review
- Design, synthesis and biological evaluation of a series of CNS penetrant HDAC inhibitors structurally derived from amyloid-β probes.Scientific reports · 2019Article
- Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms.Redox biology · 2019Review
- Lactate is an antidepressant that mediates resilience to stress by modulating the hippocampal levels and activity of histone deacetylases.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach involving the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET imaging in the baboon model and using the imaging derived data on BBB penetration from each compound to feed back into the design process. A total of 17 compounds were evaluated, revealing molecules with both high binding affinity and BBB permeability. A key element conferring BBB penetration in this benzamide series was a basic benzylic amine. These derivatives exhibited 1-100 nM inhibitory activity against recombinant human HDAC1 and HDAC2. Three of the carbon-11 labeled aminomethyl benzamide derivatives showed high BBB penetration (∼0.015%ID/cc) and regional binding heterogeneity in the brain (high in thalamus and cerebellum). Taken together this approach has afforded a strategy and a predictive model for developing highly potent and BBB permeable HDAC inhibitors for CNS applications and for the discovery of novel candidate molecules for small molecule probes and drugs.
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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.