Delayed and prolonged histone hyperacetylation with a selective HDAC1/HDAC2 inhibitor

…, P Harrington, C Hamblett, P Siliphaivanh…

文献索引：Methot, Joey L.; Hoffman, Dawn Mampreian; Witter, David J.; Stanton, Matthew G.; Harrington, Paul; Hamblett, Christopher; Siliphaivanh, Phieng; Wilson, Kevin; Hubbs, Jed; Heidebrecht, Richard; Kral, Astrid M.; Ozerova, Nicole; Fleming, Judith C.; Wang, Hongmei; Szewczak, Alexander A.; Middleton, Richard E.; Hughes, Bethany; Cruz, Jonathan C.; Haines, Brian B.; Chenard, Melissa; Kenific, Candia M.; Harsch, Andreas; Secrist, J. Paul; Miller, Thomas A. ACS Medicinal Chemistry Letters, 2014 , vol. 5, # 4 p. 340 - 345

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被引用次数: 4

摘要

The identification and in vitro and in vivo characterization of a potent SHI-1: 2 are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone hyperacetylation and gene expression changes were also observed in cell culture, and histone acetylation was observed in vivo beyond disappearance of drug from plasma. In vivo studies further demonstrated that ...