| 中文名称: | TW-37 | ||||
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| 英文名称: | TW-37 | ||||
| 别名: | N-(4-((2-(叔丁基)苯基)磺酰基)苯基)-2,3,4-三羟基-5-(2-异丙基苄基)苯甲酰胺;N-[4-(2-叔丁基苯磺酰基)苯基]-2,3,4-三羟基-5-(2-异丙基苯基甲基)苯甲酰胺;N-[4-(2-叔丁基苯磺酰基)苯基]-2,3,4-三羟基-5-(2-异丙基苄基)苯甲酰胺;TW-37 抑制剂 TW-37;N-(4-((2-(tert-butyl)phenyl)sulfonyl)phenyl)-2,3,4-trihydroxy-5-(2-isopropylbenzyl)benzamide;N-[4-(2-tert-butylphenyl)sulfonylphenyl]-2,3,4-trihydroxy-5-[(2-propan-2-ylphenyl)methyl]benzamide;N-[4-(2-TERT-BUTYLPHENYLSULFONYL)PHENYL]-2,3,4-TRIHYDROXY-5-(2-ISOPROPYLBENZYL)BENZAMIDE;TW 37;TW-37 (TW 37) | ||||
| CAS No: | 877877-35-5 | 分子式: | C33H35NO6S | 分子量: | 573.7 |
| CAS No: | 877877-35-5 | ||||
| 分子式: | C33H35NO6S | ||||
| 分子量: | 573.7 | ||||
基本信息
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产品编号：T10747 |
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产品名称：TW-37 |
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CAS: |
877877-35-5 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
六个月 |
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分子量 |
573.70 |
-20℃ |
一个月 |
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化学名： |
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Solubility (25°C) |
体外 |
DMSO |
115mg/mL (200.45mM) |
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Ethanol |
4mg/mL (6.97mM) |
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Water |
Insoluble |
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体内（现配现用） |
30% propylene glycol, 5% Tween 80, 65% D5W |
30mg/mL |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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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。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
1.7431mL |
8.7154mL |
17.4307mL |
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5mM |
0.3486mL |
1.7431mL |
3.4861mL |
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10mM |
0.1743mL |
0.8715mL |
1.7431mL |
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50mM |
0.0349mL |
0.1743mL |
0.3486mL |
生物活性
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产品描述 |
一种有效的 Bcl-2 抑制剂，作用于 Mcl-1，Bcl-2 和 Bcl-xL，Ki 值分别为 260，290 和 1110nM。 |
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靶点/IC50 |
Mcl-1 |
Bcl-2 |
Bcl-xL |
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0.26μM(Ki) |
0.29μM(Ki) |
1.11μM(Ki) |
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体外研究 |
TW-37 (TW37) is a novel nonpeptide small-molecule inhibitor designed using a structure-based design strategy. TW-37 targets the BH3-binding groove in Bcl-2 where proapoptotic Bcl-2 proteins, such as Bak, Bax, and Bid bind. In fluorescence polarization-based binding assays using recombinant Bcl-2 and Bcl-xL proteins, TW-37 binds to Bcl-2 and Bcl-xL with Ki values of 290 and 1110nM, respectively. TW-37 has an IC50 of 1.8μM for endothelial cells but shows no cytotoxic effects for fibroblasts at concentrations up to 50μM. The mechanism of TW-37-induced endothelial cell death is apoptosis, in a process mediated by mitochondrial depolarization and activation of caspase-9 and caspase-3. The effect of TW-37 on endothelial cell apoptosis is not prevented by coexposure to the growth factor milieu secreted by tumor cells. Inhibition of the angiogenic potential of endothelial cells (i.e., migration and capillary sprouting assays) and expression of the angiogenic chemokines CXCL1 and CXCL8 are accomplished at subapoptotic TW-37 concentrations (0.005-0.05μM). TW-37 is a potent Bcl-2 and Mcl-1 inhibitor. In fluorescence polarization-based binding assays using recombinant Bcl-2, Bcl-xL, and Mcl-1 proteins, TW37 binds to Bcl-2, Bcl-xL, and Mcl-1 with Ki values of 290, 1,110 and 260nM,respectively.A murine model of humanized vasculature is used to investigate the biological effect of TW-37 (TW37) on human microvascular endothelial cell in vivo. Using this model, a significant decrease is observed in total blood vessel number (P<0.05) comparing both 3 and 30mg/kg TW-37 against vehicle control. In addition to reduction in total number of blood vessels, an unusual number of occluded vessels are occurring in the treated groups. The levels of vessel occlusion are assessed by counting completely blocked vessels and determining their number as a percentage of total vessel number. TW37 concentration mediates a significant increase in the number of occluded vessels when compared with control.
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体内研究 |
A murine model of humanized vasculature is used to investigate the biological effect of TW-37 (TW37) on human microvascular endothelial cell in vivo. Using this model, a significant decrease is observed in total blood vessel number (P<0.05) comparing both 3 and 30mg/kg TW-37 against vehicle control. In addition to reduction in total number of blood vessels, an unusual number of occluded vessels are occurring in the treated groups. The levels of vessel occlusion are assessed by counting completely blocked vessels and determining their number as a percentage of total vessel number. TW37 concentration mediates a significant increase in the number of occluded vessels when compared with control. |
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推荐实验方法(仅供参考)
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细胞实验: |
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The sulforhodamine B (SRB) cytotoxicity assay is used. Briefly, optimal cell density for cytotoxicity assay, 2×104 to 3×104 cells per well, is determined by growth curve analysis. HDMECs are seeded at 2.5×104 per well in a 96-well plate and allowed to adhere overnight. Drug or control is diluted in EGM2-MV and layered onto cells, which are allowed to incubate for times as indicated in the figures. Alternatively, HDMECs are coincubated with TW-37 and 0 to 100ng/mL recombinant human VEGF (rhVEGF)165 or 0 to 100ng/mL recombinant human CXCL8. Cells are fixed on the plates by addition of cold trichloroacetic acid (10% final concentration) and incubation for 1 hour at 4℃. Cellular protein is stained by addition of 0.4% SRB in 1% acetic acid and incubation at room temperature for 30 minutes. Unbound SRB is removed by washing with 1% acetic acid and the plates are air dried. Bound SRB is resolubilized in 10mM unbuffered Tris-base and absorbance is determined on a microplate reader at 560nm. Test results are normalized against initial plating density and drug-free controls. Data are obtained from triplicate wells per condition and are representative of at least three independent experiments. |
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动物实验: |
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Mice Porous poly L-lactic acid scaffolds (6×6×1 mm) with an average pore diameter of 180μm are fabricated. Just before implantation, scaffolds are seeded with 1×106 HDMECs in a 1:1 Matrigel/EGM2-MV mix. Male severe combined immunodeficient (SCID) mice (CB.17.SCID) are anesthetized with ketamine and xylazine, and two scaffolds are implanted s.c. in the dorsal region of each mouse. At 10 days after transplantation, six mice per treatment are treated with 3mg/kg or 30mg/kg TW-37 (in vehicle: PBS/Tween 80/ethanol) or vehicle alone i.v. for 5 consecutive days.At the end of the treatment period, mice are euthanized, and the scaffolds are retrieved,fixed overnight in 10% buffered formaldehyde at 4°C, and mounted on glass slides.Immunohistochemistry is done for Factor VIII and microvessels are counted in 6 fields per scaffold and 12 scaffolds per treatment at ×200 magnification. Alternatively, sections are stained with H&E and occluded blood vessels are counted. |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
