PCI-34051 is an effective and selective HDAC8 inhibitor (IC50: 10 nM).

HDAC8:10 nM

PCI-34051对HDAC8具有良好的活性（Ki: 10 nM），并且相较于其他一类HDACs（包括HDAC1）显示出约5倍的高特异性。与HDAC1/6相比，PCI-34051的选择性高达200倍；与HDAC2/3//10相比，选择性更是高出1000倍。在对卵巢肿瘤细胞系OVCAR-3的研究中，PCI-34051展示出6 μM的GI50值和15%的细胞死亡率。在处理敏感细胞系时，24小时内或更早时间点，观察不到明显的微管蛋白或组蛋白乙酰化（<25 μM）。PCI-34051诱导的凋亡依赖于卡斯帕斯；在用5 μM PCI-34051处理后的不同时间点测量卡斯帕斯-3活性时，从12小时到24小时再到48小时，活性呈现增加趋势。PCI-34051不促进Bid蛋白的裂解。而J.RT3-T.5和P116对PCI-34051敏感，缺乏PLCγ1的J.gamma1细胞线则明显减少了PCI-34051诱导的凋亡程度。此外，稳态钙水平强烈影响PCI-34051诱导的凋亡。PCI-34051促使细胞色素c从线粒体释放。

给予PCI-34051和Dexamethasone可以减少哮喘中的嗜酸性炎症和气道高反应性，从而减少气道重塑[2]。

Histone deacetylase activity:For PCI-34051 characterization, measurements are performed in a reaction volume of 100 μL using 96-well assay plates in a fluorescence plate reader. For each isozyme. The HDAC protein in reaction buffer (50 mM HEPES, 100 mM KCl, 0.001% Tween-20, 5% dimethyl sulfoxide, pH7.4, supplemented with bovine serum albumin at concentrations of 0-0.05%) is mixed with PCI-34051 at various concentrations and allowed to incubate for 15 min. Trypsin is added to a final concentration of 50 nM, and acetyl-Gly-Ala-(N-acetyl-Lys)-amino-4-methyl coumarin is added to a final concentration of 25-100 μM to initiate the reaction. After a 30 min lag time, the fluorescence is measured over a 30 min time frame using an excitation wavelength of 335 nm and a detection wavelength of 460 nm. The increase in fluorescence with time is used as the measure of the reaction rate.

Cell lines: A549 cell line,Ovcar-3 cell line. Concentrations: 5 μM. Incubation Time: 24 hours. Method: Tumor cell lines and human umbilical vein endothelial cells are cultured for at least two doubling times,and growth is monitored at the end of PCI-34051 exposure using an Alamar Blue fluorometric cell proliferation assay as recommended by the manufacturer.PCI-34051 is assayed in triplicate wells in 96-well plates.The concentration required to inhibit cell growth by 50% (GI50) and 95% confidence intervals are estimated from the nonlinear regression using a four-parameter logistic equation.