Journal
NATURE CHEMICAL BIOLOGY
Volume 6, Issue 3, Pages 238-243Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.313
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Funding
- US National Cancer Institute [1K08CA128972]
- American Society of Hematology
- Multiple Myeloma Research Foundation
- Burroughs-Wellcome Foundation
- US National Institutes of Health [T32CA079443, 1R01DA028301-01, P01CA078048]
- US National Science Foundation [0733029, ITR 0331453]
- US National Cancer Institute's Initiative for Chemical Genetics [N01-CO-12400]
- Direct For Biological Sciences
- Division Of Environmental Biology [0733029] Funding Source: National Science Foundation
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The broad study of histone deacetylases in chemistry, biology and medicine relies on tool compounds to derive mechanistic insights. A phylogenetic analysis of class I and II histone deacetylases (HDACs) as targets of a comprehensive, structurally diverse panel of inhibitors revealed unexpected isoform selectivity even among compounds widely perceived as nonselective. The synthesis and study of a focused library of cinnamic hydroxamates allowed the identification of, to our knowledge, the first nonselective HDAC inhibitor. These data will guide a more informed use of HDAC inhibitors as chemical probes and therapeutic agents.
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