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Inhibition of Histone Demethylases by 4‐Carboxy‐2,2′‐Bipyridyl Compounds
Author(s) -
Chang KaiHsuan,
King Oliver N. F.,
Tumber Anthony,
Woon Esther C. Y.,
Heightman Tom D.,
McDonough Michael A.,
Schofield Christopher J.,
Rose Nathan R.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100026
Subject(s) - histone , epigenetics , ic50 , lysine , chemistry , lead compound , stereochemistry , structure–activity relationship , biochemistry , in vitro , biology , gene , amino acid
Exploiting epigenetics: 2‐Oxoglutarate (2OG)‐dependent histone lysine demethylases, such as JMJD2E, are potential therapeutic targets in a range of diseases. Through structure–activity relationship studies and analyses, we identified a potent 4‐carboxy‐2,2′‐bipyridyl compound, which inhibits JMJD2E with an IC 50 value of 110 n M , representing a 66‐fold improvement over the lead compound. These bipyridyl derivatives bind in the 2‐oxoglutarate binding site.