Unknown

Dataset Information

0

Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2 Inhibitor.

ABSTRACT: 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 continuous target inhibition was well tolerated and efficacious in tumor-bearing mice, leading to tumor growth inhibition with either once-daily or intermittent administration.

SUBMITTER: Methot JL 

PROVIDER: S-EPMC4027730 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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 continuous target inhibition was well tolerated and effi  ...[more]

Similar Datasets

Unknown Selective HDAC1/HDAC2 inhibitors induce neuroblastoma differentiation.
| S-EPMC3919449 | biostudies-literature
Unknown Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation.
| S-EPMC2889513 | biostudies-literature
Unknown Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing.
| S-EPMC6954403 | biostudies-literature
Unknown CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
| S-EPMC4346201 | biostudies-literature
Unknown Selective Inhibition of HDAC1 and HDAC2 as a Potential Therapeutic Option for B-ALL.
| S-EPMC4433811 | biostudies-literature
Unknown Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
| S-EPMC303344 | biostudies-other
Unknown Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease.
| S-EPMC2906581 | biostudies-literature
Unknown Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development.
| S-EPMC3286984 | biostudies-literature
Unknown Kinetically Selective Inhibitors of Histone Deacetylase 2 (HDAC2) as Cognition Enhancers.
| S-EPMC4310013 | biostudies-literature
Unknown Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis.
| S-EPMC2928690 | biostudies-literature