Romidepsin 是具有抗肿瘤活性的组蛋白去乙酰化酶 (HDAC) 抑制剂，抑制 HDAC1，HDAC2，HDAC4 和 HDAC6，IC50值分别为 36 nM，47 nM，510 nM 和 1.4 μM。它由紫色杆菌产生，诱导 G2/M 细胞周期阻滞和凋亡。它用于难治性或复发性皮肤和外周 T 细胞淋巴瘤。

Romidepsin is an intravenously administered histone deacetylase inhibitor and antineoplastic agent that is approved for use in refractory or relapsed cutaneous and peripheral T cell lymphomas.

Romidepsin剂量依赖性抑制免疫功能低下的小鼠中皮下NB 异种移植的生长.在NB病人的肿瘤组织中Romidepsin会诱导某些基因的表达,如 p21 和p75 以及NTRK (TrkA).与PBS处理的对照组相比,单独使用Romidepsin和埃罗替尼分别可以对NCI-H1299细胞系的异种移植生长抑制到72%和43%,但是并不具有明显的统计学意义.只有当两种药物联用的时候才会对其生长造成明显的抑制作用,此时生长抑制到28%.每周两次0.1-1 mg/kg Romidepsin的给药显著延长携带U-937淋巴瘤的小鼠的存活时间,平均存活时间为30.5（0.56 mg/kg）和33天（0.32 mg/kg）,对照组小鼠为20天.

Romidepsin处理72小时可以抑制人NB肿瘤细胞系的生长,而NIH3T3细胞系并不受影响。Romidepsin对于单拷贝或N-myc多拷贝的NB细胞系以及含有正常或突变的p53和含有Alk突变体的细胞系都有剂量依赖性的选择性细胞毒性。Romidepsin抑制NSCLC细胞系生长,IC50范围从1.3 ng/mL到4.9 ng/mL。Romidepsin可以降低埃罗替尼对NSCLC细胞系的IC50值,增加NSCLC细胞系对埃罗替尼的敏感性。Romidepsin在抑制A549细胞增殖方面比TSA效力强100倍,比丁酸强100万倍。Romidepsin抑制U-937,K562和CCRF-CEM细胞的生长,IC50分别为5.92 nM,8.36 nM和6.95 nM。

HDAC-inhibitory activity: For the enzyme assay, 10 μL of [3H]acetyl-labeled histones (25,000 cpm/10 μg) are added to 90 μL of the HDAC enzyme fraction extracted from 293T cells overexpressing HDAC1 or HDAC2 in the presence of increasing concentrations of Romidepsin, and the mixture is incubated at 37 °C for 15 minutes. The enzyme reaction is linear for at least 1 hour. The reaction is stopped by the addition of 10 μL of concentrated HCl. The released [3H]acetic acid is extracted with 1 mL of ethylacetate, and 0.9 mL of the solvent layer is taken into 5 mL of aqueous counting scintillant II solution for determination of radioactivity. The IC50 values are determined from at least three independent dose-response curves.

Cells are exposed to various concentrations of Romidepsin for 72 hours in 96-well plates. 20 μL of 5 mg/mL MTT solution in PBS is added to each well for 4 hours. After removal of the medium, 170 μL of DMSO is added to each well to dissolve the formazan crystals. The absorbance at 540 nm is determined. In addition, cells are incubated with trypan blue, and the numbers of blue (dead) cells and transparent (live) cells are counted in a hemocytometer. For cell cycle analysis, cells are incubated for 30 minutes in propidium iodide staining solution containing 0.05 mg/mL propidium iodide, 1 mM EDTA, 0.1% Triton X-100, and 1 mg/mL RNase A in PBS. The suspension is then passed through a nylon mesh filter and analyzed on a Becton Dickinson FACScan. (Only for Reference)

128517-07-7

C24H36N4O6S2

540.69

FK 228;FR 901228;罗米地辛;Depsipeptide;NSC 630176

DMSO:5.4 mg/mL (10 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years