Droxinostat (NS 41080) is a selective inhibitor of HDAC, mostly for HDACs 6 and 8 with IC50 of 2.47 μM and 1.46 μM, greater than 8-fold selective against HDAC3 and no inhibition to HDAC1, 2, 4, 5, 7, 9, and 10.

HDAC6:2.47 μM, HDAC8:1.46 μM

Droxinostat最初被识别为通过下调c-Fas相关死亡结构域样白介素-1转化酶样抑制蛋白（c-FLIP）的表达，使PPC-1细胞对FAS和TRAIL敏感化。[1] 在悬浮培养而非贴壁条件下，Droxinostat（20 μM–60 μM）首先通过激活caspase 8，随后激活线粒体途径，使PPC-1细胞对细胞外基质脱附引发的细胞死亡（anoikis）敏感。同样，Droxinostat也使包括PC-3、DU-145、T47D和OVCAR-3等其他癌细胞系对细胞外基质脱附引发的细胞死亡或CH-11诱导的凋亡敏感化，但对LNCaP或MB-MDA-468则没有这种作用。[2] 然而，直到最近Droxinostat的直接靶标仍是一个谜。研究揭示，在组蛋白去乙酰化酶（HDAC）1-10亚型中，Droxinostat选择性抑制HDAC3、6和8，其IC50值分别为16.9 μM、2.47 μM和1.46 μM，而对其他HDAC成员的抑制（IC50 > 20 μM）没有影响。[3] 在MCF-7乳腺癌细胞中，Droxinostat（10 μM–100 μM）通过减少c-FLIPL和c-FLIPS的表达，降低细胞存活率，并诱导凋亡，从而使细胞对凋亡敏感化。[4]

在SCID小鼠模型中，处理了Droxinostat (30 μM)的PPC-1细胞与未处理细胞相比，远处肿瘤形成的减少。[2]

HDAC Inhibition Assay: HDAC inhibition is assessed using the CycLex HDACs fluorometric assay according to the manufacturer's protocol and using crude nuclear extract from HeLa cells (principally HDAC1 and HDAC2). The relative activity is expressed as (fluorescence intensity of treated samples/fluorescence intensity of controls) × 100

PPC-1 cells (1 × 104) are seeded overnight into 96-well flat-bottomed plates in 100 μL of medium containing 2.5% FCS. The next day, Droxinostat is added. CH-11 antibody (100 ng/mL) is then added and the cells are incubated for 24 hours before assessing cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye reduction assay.(Only for Reference)