| 产品介绍 |
PCI-34051 is a potent and selective inhibitor of histone deacetylase 8 (HDAC8) with an IC50 ~10 nM. It displays >200 fold selectivity over other HDAC isoforms 1, 2, 3, 6 and 10. PCI-34051 has a unique mechanism of action involving PLCgamma1 activation and calcium-induced apoptosis, and could offer benefits including a greater therapeutic index for treating T-cell malignancies. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemia, but not in other hematopoietic or solid tumor lines. Unlike broad-spectrum HDAC inhibitors, PCI-34051 does not cause detectable histone or tubulin acetylation. Cells defective in T-cell receptor signaling were still sensitive to PCI-34051-induced apoptosis, whereas a phospholipase C-gamma1 (PLCgamma1)-defective line was resistant. In addition, steady-state calcium levels strongly influence the apoptosis induced by PCI-34051. It also induces cytochrome c release from mitochondria.
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