Mocetinostat (MGCD0103) is a potent, orally active and isotype-selective HDAC (Class I/IV) inhibitor with IC₅₀s of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively. Mocetinostat shows no inhibition on HDAC4, HDAC5, HDAC6, HDAC7, or HDAC8.

Mocetinostat is a potent, orally active and isotype-selective HDAC (Class I/IV) inhibitor with IC₅₀s of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively. Mocetinostat shows no inhibition on HDAC4, HDAC5, HDAC6, HDAC7, or HDAC8. Mocetinostat (MGCD0103) exhibits potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity is required for these effects. In all cell lines tested, Mocetinostat (MGCD0103) partially inhibits cellular HDAC enzyme activity although the maximal inhibition of activity varies among cell lines from 75% to 85% of total activity. The IC₅₀ of Mocetinostat in intact cancer cells is independent of tissue origin. In A549 cells, MGCD0103 shows dose-dependent inhibition of HDAC activity in whole cells. At high concentrations in A549 cells, Mocetinostat inhibits a maximum of 80% of total activity. In HCT116 cells, Mocetinostat induces a significant S-phase depletion and both G₁ and G₂-M accumulation^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mocetinostat (MGCD0103) significantly inhibits growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. The p.o. administration of Mocetinostat (MGCD0103) (2HBr salt) significantly reduces growth of implanted advanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration. Mocetinostat (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blocks growth of tumors compared with vehicle treatment alone (P<0.05 in post-ANOVA Dunnett's test) with no change in body weight^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

396.44

C₂₃H₂₀N₆O

726169-73-9

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL (126.12 mM; Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
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• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.25 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.25 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Fournel M, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008 Apr;7(4):759-68.

  [2]. Cai J, et al. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method. Biomed Res Int. 2015;2015:517295.

Cells in 96-well plates are incubated with Mocetinostat at various concentrations for 72 h at 37°C in 5% CO₂. MTT is added at a final concentration of 0.5 mg/mL and incubated with the cells for 4 h before an equal volume of solubilization buffer [50% N,N-dimethylformamide, 20% SDS (pH 4.7)] is added. After overnight incubation, solubilized dye is quantified by reading at 570 nm using a reference at 630 nm. Absorbance values are converted to cell numbers according to a standard growth curve of the relevant cell line. The concentration which reduces cell numbers to 50% relative to DMSO-treated cells is determined as MTT IC₅₀^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[1]
Female CD-1 nude mice, ages 8 to 10 wk are used. Tumor fragments (30 mg), which have been serially passaged thrice in vivo in minimal, are implanted s.c. through a small surgical incision on the flank of the mice while under general anesthesia. Mocetinostat is dissolved in vehicle (PBS acidified with 0.1 N HCl or PEG400/0.2 N HCl saline, 40:60) and dosed p.o. as solutions daily. Tumor volumes and body weight are monitored thrice weekly for at least 2 wk. Each experimental group containe six to eight animals. For pharmacokinetic study, blood is collected from animals at various time points, and plasma samples are analyzed.
Rats^[2]
Forty rats (220±20 g) are randomly divided into four different dosages of Mocetinostat groups (Low group, Medium group, High group, and control group with 10 rats in each group). Mocetinostat is dissolved in corn oil as suspension at three different concentrations (20, 40, and 80 mg/mL). Three different Mocetinostat groups (Low group, Medium group, and High group) are respectively given Mocetinostat 20, 40, and 80 mg/kg one time by intragastric administration at every morning and last for 7 days. Control group are given saline by same administration method. At 8 days morning, six probe drugs, Bupropion, Phenacetin, Tolbutamide, Metoprolol, Testosterone, and Omeprazole, are mixed in corn oil and given to the rats of three Mocetinostat groups and control group by intragastric administration at a single dosage of 10 mg/kg for Bupropion, Phenacetin, Metoprolol, Testosterone, and Omeprazole and 1 mg/kg for Tolbutamide.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Fournel M, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008 Apr;7(4):759-68.

  [2]. Cai J, et al. The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method. Biomed Res Int. 2015;2015:517295.