生物活性
M344 shows a potent inhibition activity against histone deacetylase with IC50 of 100 nM. M344 produces a more significant effect on cell proliferation than on cell differentiation in MEL DS19 cells. M344 shows cell toxicity at concentrations above 10 μM, while a maximum of only 20% of the surviving cell population are induced to differentiate. In vitro, M344 produces the significant anti-proliferative effects on the endometrial cancer cell line Ishikawa and the ovarian cancer cell line SK-OV-3 with EC50 of 2.3 μM and 5.1 μM, respectively. While the normal human endometrial epithelial cells shows little sensitivity to M344. In addition, M344 also decreases proportion of cells in the S-phase, increases proportion in the G0/G1 phases of the cell cycle, induces apoptosis and decreases the transmembrane potential of mitochondria. M344 show the anti-proliferative activities against embryonal nervous system tumor cells including medulloblastoma cells (D341 Med, Daoy) and neuroblastoma cells (CH-LA 90,SHSY-5Y ) with GI50 of 0.65 μM, 0.63 μM, 0.63 μM and 0.67 μM, respectively.M344 (5 μM ) in combination with cisplatin (10 μg/mL) results increased induction of ATF3 and shows enhanced cytotoxic effects than cisplatin alone in a panel of human derived cancer cell lines, such as MCF-7, PC3, SK-OV3, and A549.
化学数据
| 分子量 | 307.39 |
| 分子式 | C16H25N3O3 |
| CAS号 | 251456-60-7 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 55 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | MEL DS19 cells |
| 方法 | Maintaining MEL DS19 cells (murine erythroleukemia cells) in D-MEM containing 100 units/mL penicillin G sodium and 100 μg/mL streptomycin sulfate supplemented with 10% fetal bovine serum at 37 °C in a 5% CO2 atmosphere. To test M344 for potential to induce cell differentiation, log-phase cells with a population doubling time of 11–13 hours are used. Preparing Serial dilutions of M344 in 24-well plates using 1 mL of D-MEM/well. If M344 are dissolved in DMSO, control wells contains the same amount of solvent (generally 2 μL/mL of medium). Subsequently, adding the cell suspension to the wells. After 72 hours the experiment is evaluated. Using a Casy 1 TTC flow cytometer to counte cell numbers. With the solvent control , expressing the proliferation of treated cells as percent proliferation in comparison. Differentiated MEL cells accumulate hemoglobin. Therefore, the induction of cell differentiation is determined by benzidine staining according to the literature. To 100 μL of cell suspension is added 10 μL of a 0.4% solution of benzidine in 12% acetic acid which contains 2% H2O2. Within 5 minutes hemoglobin-containing cells stains blue.Under the microscope in a hemocytometer ,counting Benzidine-positive and -negative cells , and calculating the percentage of positive cells . Testing M344 first at 10 μM and 50 μM final concentration. A range of concentrations is chosen for a dose–response analysis according to activity/toxicity profile,.
|
| 浓度 | 0 to 50 μM |
| 处理时间 | 72 hours |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.2532 mL | 16.266 mL | 32.532 mL |
| 5 mM | 0.6506 mL | 3.2532 mL | 6.5064 mL |
| 10 mM | 0.3253 mL | 1.6266 mL | 3.2532 mL |
