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BNG 3‐36 as a slow‐binding, competitive inhibitor against HDAC4 (768.19)
Author(s) -
Mueller Dustin,
Yu Junru,
Omlid Joseph,
Singh Raushan,
Leedahl Travis,
Balasubranian Narayanganesh,
Cook Gregory,
Srivastava D.K.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.768.19
Subject(s) - hdac8 , hdac4 , chemistry , histone deacetylase inhibitor , histone deacetylase , hdac1 , non competitive inhibition , biochemistry , pharmacology , enzyme , cancer research , histone , biology , gene
Histone deacetylase 4 (HDAC4) is a high priority drug target for the treatment of various human diseases including Huntington’s disease and various cancers. Pan‐HDAC inhibitors, such as Suberoylanilide Hydroxamic Acid (SAHA) have already been screened and approved by the FDA as a treatment for some forms of cancer. BNG 3‐36 is a novel, thiol based compound that binds to HDAC4 utilizing a unique slow‐binding feature, inhibiting the catalytic mechanism of the enzyme. When added to HDAC8, however, this particular inhibitor shows normal competitive features. When the inhibitor is added to HDAC8, a member of another class of HDACs, the slow‐binding feature is not seen and instead is a normal competitive. We show that the inhibitor has a slow‐binding competitive feature when used with HDAC4 and has a normal competitive feature when used with HDAC8. Grant Funding Source : Supported by the NIH