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- W2914104766 abstract "Since the discovery of compound BIX01294 over 10 years ago, only a very limited number of nonquinazoline inhibitors of H3K9-specific methyltransferases G9a and G9a-like protein (GLP) have been reported. Herein, we report the identification of a novel chemotype for G9a/GLP inhibitors, based on the underinvestigated 2-alkyl-5-amino- and 2-aryl-5-amino-substituted 3H-benzo[e][1,4]diazepine scaffold. Our research efforts resulted in the identification 12a (EML741), which not only maintained the high in vitro and cellular potency of its quinazoline counterpart, but also displayed improved inhibitory potency against DNA methyltransferase 1, improved selectivity against other methyltransferases, low cell toxicity, and improved apparent permeability values in both parallel artificial membrane permeability assay (PAMPA) and blood–brain barrier-specific PAMPA, and therefore might potentially be a better candidate for animal studies. Finally, the co-crystal structure of GLP in complex with 12a provides the basis for the further development of benzodiazepine-based G9a/GLP inhibitors." @default.
- W2914104766 created "2019-02-21" @default.
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- W2914104766 date "2019-02-12" @default.
- W2914104766 modified "2023-10-14" @default.
- W2914104766 title "Discovery of a Novel Chemotype of Histone Lysine Methyltransferase EHMT1/2 (GLP/G9a) Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Co-crystal Structure" @default.
- W2914104766 cites W1027568982 @default.
- W2914104766 cites W1484972278 @default.
- W2914104766 cites W1599834610 @default.
- W2914104766 cites W1893182892 @default.
- W2914104766 cites W1951116999 @default.
- W2914104766 cites W1967163877 @default.
- W2914104766 cites W1974343294 @default.
- W2914104766 cites W1977401216 @default.
- W2914104766 cites W1978660434 @default.
- W2914104766 cites W1980937575 @default.
- W2914104766 cites W1985180051 @default.
- W2914104766 cites W1986642686 @default.
- W2914104766 cites W1991732183 @default.
- W2914104766 cites W1995895091 @default.
- W2914104766 cites W1998883376 @default.
- W2914104766 cites W1999337138 @default.
- W2914104766 cites W2001891149 @default.
- W2914104766 cites W2005470042 @default.
- W2914104766 cites W2008266061 @default.
- W2914104766 cites W2009858080 @default.
- W2914104766 cites W2012513430 @default.
- W2914104766 cites W2015416439 @default.
- W2914104766 cites W2020084080 @default.
- W2914104766 cites W2022851859 @default.
- W2914104766 cites W2024525328 @default.
- W2914104766 cites W2028074916 @default.
- W2914104766 cites W2028764523 @default.
- W2914104766 cites W2029197798 @default.
- W2914104766 cites W2032191311 @default.
- W2914104766 cites W2032865438 @default.
- W2914104766 cites W2033027341 @default.
- W2914104766 cites W2036357556 @default.
- W2914104766 cites W2036777838 @default.
- W2914104766 cites W2037215281 @default.
- W2914104766 cites W2038275607 @default.
- W2914104766 cites W2040527067 @default.
- W2914104766 cites W2043509228 @default.
- W2914104766 cites W2045722951 @default.
- W2914104766 cites W2047552911 @default.
- W2914104766 cites W2048389974 @default.
- W2914104766 cites W2049365130 @default.
- W2914104766 cites W2050328092 @default.
- W2914104766 cites W2057321383 @default.
- W2914104766 cites W2059347029 @default.
- W2914104766 cites W2059586458 @default.
- W2914104766 cites W2063020711 @default.
- W2914104766 cites W2063296278 @default.
- W2914104766 cites W2065125513 @default.
- W2914104766 cites W2065364505 @default.
- W2914104766 cites W2067300585 @default.
- W2914104766 cites W2068865819 @default.
- W2914104766 cites W2073101936 @default.
- W2914104766 cites W2078521443 @default.
- W2914104766 cites W2079116818 @default.
- W2914104766 cites W2083284090 @default.
- W2914104766 cites W2084164320 @default.
- W2914104766 cites W2084885369 @default.
- W2914104766 cites W2086180957 @default.
- W2914104766 cites W2086708877 @default.
- W2914104766 cites W2090364875 @default.
- W2914104766 cites W2092794927 @default.
- W2914104766 cites W2095626300 @default.
- W2914104766 cites W2096083625 @default.
- W2914104766 cites W2098103685 @default.
- W2914104766 cites W2105668062 @default.
- W2914104766 cites W2106473601 @default.
- W2914104766 cites W2106903510 @default.
- W2914104766 cites W2107760271 @default.
- W2914104766 cites W2108381095 @default.
- W2914104766 cites W2108462555 @default.
- W2914104766 cites W2109184569 @default.
- W2914104766 cites W2110478240 @default.
- W2914104766 cites W2111977276 @default.
- W2914104766 cites W2115596584 @default.
- W2914104766 cites W2115630484 @default.
- W2914104766 cites W2117305571 @default.
- W2914104766 cites W2118405368 @default.
- W2914104766 cites W2122781654 @default.
- W2914104766 cites W2124026197 @default.