ArticleACS chemical biology2015
Computational design of a time-dependent histone deacetylase 2 selective inhibitor.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Targeting histone deacetylases for cancer therapy: Trends and challenges.Acta pharmaceutica Sinica. B · 2023Review
- Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline-Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Nuclear Coregulatory Complexes in Tregs as Targets to Promote Anticancer Immune Responses.Frontiers in immunology · 2022Review
- Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs).International journal of molecular sciences · 2020Review
- Review
- Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling.ACS medicinal chemistry letters · 2019Article
- Zinc binding groups for histone deacetylase inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2018Review
- Histone/protein deacetylase inhibitor therapy for enhancement of Foxp3+ T-regulatory cell function posttransplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Review
- Parametrization of Combined Quantum Mechanical and Molecular Mechanical Methods: Bond-Tuned Link Atoms.Molecules (Basel, Switzerland) · 2018Article
- Current Strategies and Applications for Precision Drug Design.Frontiers in pharmacology · 2018Review
- Chalcone Derivatives: Promising Starting Points for Drug Design.Molecules (Basel, Switzerland) · 2017Review
- CombinatorialFrontiers in molecular neuroscience · 2017Article
- Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach.Frontiers in neuroscience · 2016Article
- Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme Reactions.Methods in enzymology · 2016Article
- Thiol versus hydroxamate as zinc binding group in HDAC inhibition: An ab initio QM/MM molecular dynamics study.Journal of computational chemistry · 2015Article
- Diverse Molecular Targets for Chalcones with Varied Bioactivities.Medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Development of isoform-selective histone deacetylase (HDAC) inhibitors is of great biological and medical interest. Among 11 zinc-dependent HDAC isoforms, it is particularly challenging to achieve isoform inhibition selectivity between HDAC1 and HDAC2 due to their very high structural similarities. In this work, by developing and applying a novel de novo reaction-mechanism-based inhibitor design strategy to exploit the reactivity difference, we have discovered the first HDAC2-selective inhibitor, β-hydroxymethyl chalcone. Our bioassay experiments show that this new compound has a unique time-dependent selective inhibition on HDAC2, leading to about 20-fold isoform-selectivity against HDAC1. Furthermore, our ab initio QM/MM molecular dynamics simulations, a state-of-the-art approach to study reactions in biological systems, have elucidated how the β-hydroxymethyl chalcone can achieve the distinct time-dependent inhibition toward HDAC2.
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Registered trials
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