PCI-34051

PCI-34051 is a potent and selective inhibitor of HDAC8 with >200-fold selectivity over the other HDAC isoforms 1, 2, 3, 6 and 10 with IC50 values of 4, >50, >50, 2.9 and 13 μM, respectively. PCI-34051 induces caspase-dependent apoptosis in cell lines derived from T-cell lymphomas or leukemias (GI50s = 2.4 - 4 μM), but not in other hematopoietic or solid tumor lines. PCI-34051 does not cause detectable histone or tubulin acetylation like other broad-spectrum HDAC inhibitors. PCI-34051-induced apoptosis upon treatment with a PLC inhibitor U73122 showed a dose-dependent decrease on Jurkat cells. The mechanism by which PCI-34051 induces apoptosis in T-cell lines is also novel to the histone deacetylase field; it involves Ca2+ signaling via phospholipase C-gamma1.