Development of a histone deacetylase 6 inhibitor and its biological effects Journal Article

   


Authors: Lee, J. H.; Mahendran, A.; Yao, Y.; Ngo, L.; Venta-Perez, G.; Choy, M. L.; Kim, N.; Ham, W. S.; Breslow, R.; Marks, P. A.
Article Title: Development of a histone deacetylase 6 inhibitor and its biological effects
Abstract: Development of isoform-selective histone deacetylase (HDAC) inhibitors is important in elucidating the function of individual HDAC enzymes and their potential as therapeutic agents. Among the eleven zinc-dependent HDACs in humans, HDAC6 is structurally and functionally unique. Here, we show that a hydroxamic acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl) amino]- 2-oxoethyl)benzamide (HPOB) selectively inhibits HDAC6 catalytic activity in vivo and in vitro. HPOB causes growth inhibition of normal and transformed cells but does not induce cell death. HPOB enhances the effectiveness of DNA-damaging anticancer drugs in transformed cells but not normal cells. HPOB does not block the ubiquitin-binding activity of HDAC6. The HDAC6-selective inhibitor HPOB has therapeutic potential in combination therapy to enhance the potency of anticancer drugs.
Keywords: controlled study; histone deacetylase inhibitor; nonhuman; ubiquitin; binding affinity; mouse; animal tissue; drug inhibition; etoposide; animal experiment; in vivo study; drug potency; in vitro study; drug effect; drug discovery; cell transformation; vorinostat; ic 50; tubacin; anticancer agents; histone deacetylase 6; epigenetics-based chemotherapy; ricolinostat
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 110
Issue: 39
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2013-09-24
Start Page: 15704
End Page: 15709
Language: English
DOI: 10.1073/pnas.1313893110
PROVIDER: scopus
PMCID: PMC3785767
PUBMED: 24023063
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84884631782&partnerID=40&md5=2971611918ee6e51a711fb0cc23d24b2
Notes: --- - "Export Date: 1 November 2013" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Lang Ngo
    27 Ngo
  2. Gisela Venta-Perez
    23 Venta-Perez
  3. Ju-Hee Lee
    9 Lee
  4. Megan Lee Choy
    6 Choy
  5. Paul Marks
    186 Marks
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