规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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1g |
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Other Sizes |
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靶点 |
ACAT1 (IC50 = 24 μM); ACAT2 (IC50 = 9.2 μM)
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体外研究 (In Vitro) |
当给予阿伐麦布(0、0.25、5、10、20、40和80μM;1、2和3天)时,前列腺癌(PCa)细胞增殖较少[2]。 β-连环蛋白、波形蛋白、N-钙粘蛋白、Snail 和 MMP9 的表达(所有这些都与上皮间质转化 (EMT) 密切相关)被阿瓦西贝(10 和 20 μM;48 小时)降低 [2] 。在前列腺癌中,avasimibe(10 和 20 μM)通过 E2F-1 信号通路诱导细胞周期停滞。在 PCa 细胞中,avasimibe 导致 G1 期细胞周期停滞 [2]。阿伐麦布(10 和 20 μM)可抑制 PCa 细胞转移 [2]。
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体内研究 (In Vivo) |
在七周内,avasimibe(每隔一天腹腔注射 30 mg/kg)可抑制体内 PCa 细胞的发育和转移。阿瓦西米毒性极小,具有良好的生物相容性[2]。
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细胞实验 |
细胞活力测定[2]
细胞类型: PCa 细胞(PC-3 和 DU 145) 测试浓度: 0、0.25、5、10、 20、40 和 80 µM 孵育时间:1、2 和 3 天 实验结果:剂量依赖性抑制 PC-3 和 DU 145 细胞活力。 蛋白质印迹分析[2] 细胞类型: PCa 细胞(PC-3 和 DU 145) 测试浓度: 10 和20 µM 孵育持续时间: 48 小时 实验结果:降低 EMT 相关蛋白(β-连环蛋白、波形蛋白、N-钙粘蛋白、Snail、MMP9 和 E-钙粘蛋白)。 细胞周期分析[2] 细胞类型: PCa 细胞(PC-3 和 DU 145) 测试浓度: 10 和20 µM 孵育时间: 48 小时 实验结果:诱导 G1 期周期停滞并改变 PCa 细胞中 G1 期相关蛋白水平。 |
动物实验 |
Animal/Disease Models: SPF male mice (BALB/c-nude, 4 weeks old) bearing PCa cells[2]
Doses: 30 mg/kg Route of Administration: Intraperitoneally injected for 7 weeks Experimental Results: decreased tumor volume compared with that of the control group. Inhibited PCa growth and migration in vivo. |
参考文献 |
[1]. Taichi Ohshiro,et al. Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1108-15.
[2]. Kangping Xiong, et al. The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer.Cancer Cell Int. 2021 Aug 30;21(1):461. |
其他信息 |
Avasimibe is an orally bioavailable inhibitor of acyl-Coenzyme A:cholesterol acyltransferase (ACAT) that prevents cholesterol deposition in the arterial wall. Research was discontinued due to difficulties in assaying the effects of avasimibe on preventing plaque formation and due to its ability to increase the activity of Cytochrome P450 3A4, thus increasing the removal of other drugs from the body.
Background: New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer. Methods: In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model. Results: The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, β-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group. Conclusions: Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment. |
分子式 |
C29H43NO4S
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分子量 |
501.72
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精确质量 |
501.291
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元素分析 |
C, 69.42; H, 8.64; N, 2.79; O, 12.76; S, 6.39
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CAS号 |
166518-60-1
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相关CAS号 |
166518-61-2 (sodium);166518-60-1 (free form);
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PubChem CID |
166558
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外观&性状 |
Typically exists as white to off-white solids at room temperature
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密度 |
1.1±0.1 g/cm3
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熔点 |
178-180° (Lee); mp 169.5-170.4° (Dozeman)
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折射率 |
1.529
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LogP |
9.34
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tPSA |
80.85
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SMILES |
S(N([H])C(C([H])([H])C1C(=C([H])C(C([H])(C([H])([H])[H])C([H])([H])[H])=C([H])C=1C([H])(C([H])([H])[H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)(=O)(=O)OC1C(=C([H])C([H])=C([H])C=1C([H])(C([H])([H])[H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H]
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InChi Key |
PTQXTEKSNBVPQJ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C29H43NO4S/c1-17(2)22-14-25(20(7)8)27(26(15-22)21(9)10)16-28(31)30-35(32,33)34-29-23(18(3)4)12-11-13-24(29)19(5)6/h11-15,17-21H,16H2,1-10H3,(H,30,31)
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化学名 |
((2,4,6-Tris(1-methylethyl)phenyl)acetyl)sulfamic acid 2,6-bis(1-methylethyl)phenyl ester
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别名 |
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外实验) |
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溶解度 (体外实验) |
配方 1 中的溶解度: 7.5 mg/mL (14.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 悬浮液;超声助溶。
例如,若需制备1 mL的工作液,可将100 μL 75.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中,混匀;然后向上述溶液中加入50 μL Tween-80,混匀;加入450 μL生理盐水定容至1 mL。 *生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 配方 2 中的溶解度: 7.5 mg/mL (14.95 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 悬浊液; 超声助溶。 例如,若需制备1 mL的工作液,可将 100 μL 75.0mg/mL澄清的DMSO储备液加入到900μL 20%SBE-β-CD生理盐水中,混匀。 *20% SBE-β-CD 生理盐水溶液的制备(4°C,1 周):将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中,得到澄清溶液。 View More
配方 3 中的溶解度: 7.5 mg/mL (14.95 mM) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液; 超声助溶. 配方 4 中的溶解度: 2% DMSO+corn oil: 5mg/mL 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9931 mL | 9.9657 mL | 19.9314 mL | |
5 mM | 0.3986 mL | 1.9931 mL | 3.9863 mL | |
10 mM | 0.1993 mL | 0.9966 mL | 1.9931 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
计算结果:
工作液浓度: mg/mL;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。