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Search Results (2)

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Authors = Martijn R. H. Zwinderman

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25 pages, 1455 KiB  
Review
Targeting HDAC Complexes in Asthma and COPD
by Martijn R. H. Zwinderman, Sander de Weerd and Frank J. Dekker
Epigenomes 2019, 3(3), 19; https://doi.org/10.3390/epigenomes3030019 - 7 Sep 2019
Cited by 40 | Viewed by 7677
Abstract
Around three million patients die due to airway inflammatory diseases each year. The most notable of these diseases are asthma and chronic obstructive pulmonary disease (COPD). Therefore, new therapies are urgently needed. Promising targets are histone deacetylases (HDACs), since they regulate posttranslational protein [...] Read more.
Around three million patients die due to airway inflammatory diseases each year. The most notable of these diseases are asthma and chronic obstructive pulmonary disease (COPD). Therefore, new therapies are urgently needed. Promising targets are histone deacetylases (HDACs), since they regulate posttranslational protein acetylation. Over a thousand proteins are reversibly acetylated, and acetylation critically influences aberrant intracellular signaling pathways in asthma and COPD. The diverse set of selective and non-selective HDAC inhibitors used in pre-clinical models of airway inflammation show promising results, but several challenges still need to be overcome. One such challenge is the design of HDAC inhibitors with unique selectivity profiles, such as selectivity towards specific HDAC complexes. Novel strategies to disrupt HDAC complexes should be developed to validate HDACs further as targets for new anti-inflammatory pulmonary treatments. Full article
(This article belongs to the Special Issue Complex Disease Epigenetics)
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13 pages, 2941 KiB  
Review
The Process and Strategy for Developing Selective Histone Deacetylase 3 Inhibitors
by Fangyuan Cao, Martijn R. H. Zwinderman and Frank J. Dekker
Molecules 2018, 23(3), 551; https://doi.org/10.3390/molecules23030551 - 2 Mar 2018
Cited by 50 | Viewed by 7612
Abstract
Histone deacetylases (HDACs) are epigenetic drug targets that have gained major scientific attention. Inhibition of these important regulatory enzymes is used to treat cancer, and has the potential to treat a host of other diseases. However, currently marketed HDAC inhibitors lack selectivity for [...] Read more.
Histone deacetylases (HDACs) are epigenetic drug targets that have gained major scientific attention. Inhibition of these important regulatory enzymes is used to treat cancer, and has the potential to treat a host of other diseases. However, currently marketed HDAC inhibitors lack selectivity for the various HDAC isoenzymes. Several studies have shown that HDAC3, in particular, plays an important role in inflammation and degenerative neurological diseases, but the development of selective HDAC3 inhibitors has been challenging. This review provides an up-to-date overview of selective HDAC3 inhibitors, and aims to support the development of novel HDAC3 inhibitors in the future. Full article
(This article belongs to the Special Issue Modulators of Histone Acetylation: A Medicinal Chemistry Perspective)
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