PCI-34051

PCI-34051 is a potent and highly selective small molecule **inhibitor of histone deacetylase 8 (HDAC8)**, exhibiting over 200-fold selectivity for HDAC8 over other HDAC isoforms (HDAC1, 2, 3, 6, and 10)[1][3][7]. It induces **caspase-dependent apoptosis in T-cell lymphoma and leukemia cells**, with minimal effect on normal hematopoietic cells[3][7][10]. PCI-34051's pro-apoptotic effect is mechanistically linked to **activation of PLCgamma1 and rapid intracellular Ca2+ mobilization**, followed by mitochondrial cytochrome c release and cell death[7]. Unlike pan-HDAC inhibitors, it does not cause detectable hyperacetylation of histones or tubulin[1][3][7]. PCI-34051 shows therapeutic promise in hematologic malignancies (especially T-cell lymphoma and leukemia) and has also demonstrated anticancer activity (including synergy in combination regimens) in preclinical models of ovarian cancer[2][5][10]. It is used as a research tool and is not approved for clinical use[1][7].

Other names

N-Hydroxy-1-[(4-methoxyphenyl)methyl]-1H-indole-6-carboxamide