Usage
PCI-34051 is a potent, histone deacetylase 8 (HDAC8)-specific inhibitor. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemias. PCI-34051 did not affect other hematopoietic or solid tumor lines. PCI-34051 treatment has been shown to significantly reduce cholesterol accumulation in Niemann-Pick type C1 gene mutated human fibroblast.
Uses
PCI-34051 is a potent, histone deacetylase 8 (HDAC8)-specific inhibitor. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemias. PCI-34051 did not affect other hematopoietic or solid tumor lines. PCI-34051 treatment has been shown to significantly reduce cholesterol accumulation in Niemann-Pick type C1 gene mutated human fibroblast.
Definition
ChEBI: N-hydroxy-1-[(4-methoxyphenyl)methyl]-6-indolecarboxamide is an indolecarboxamide.
Biological Activity
pci-34051 is a potent, specific inhibitor of histone deacetylase 8 (hdac8) with greater than 200-fold selectivity over the other hdac isoforms, such as 1, 2, 3, 6 and 10. it induces caspase dependent apoptosis in cell lines derived from t-cell lymphomas or leukemias, but not in other hematopoietic or solid tumor lines. pci-34051 does not cause detectable histone or tubulin acetylation and also does not inhibit growth or induce apoptosis in normal cells such as pbmcs or fibroblasts. although a phospholipase c-gamma1 (plcgamma1) defective line is resistant, cells defective in t-cell receptor signaling are still sensitive to pci-34051 induced apoptosis.
in vivo
Administration of PCI-34051 and Dexamethasone reduces the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling[2].
IC 50
HDAC8: 10 nM (IC50); HDAC6: 2.9 μM (IC50); HDAC1: 4 μM (IC50); HDAC10: 13 μM (IC50)
References
[1]. s balasubramanian, j ramos, w luo, m sirisawad, e verner, j j buggy. a novel histone deacetylase 8 (hdac8)-specific inhibitor pci-34051 induces apoptosis in t-cell lymphomas. leukemia (2008) 22, 1026–1034.
[2]. sriram balasubramanian, erik verner, joseph j. buggy. isoform-specific histone deacetylase inhibitors: the next step? cancer letters. volume 280, issue 2, 8 august 2009, pages 211–221.
