Encequidar mesylate (HM30181 (mesylate))
(Synonyms: HM30181 mesylate; HM30181A mesylate) 目录号 : GC33185
HM30181 mesylate salt, a tetrazole derivative, is known as a P-glycoprotein inhibitor that has inhibitory activities on multidrug resistance in cancer cells.
Cas No.:849675-87-2
Sample solution is provided at 25 µL, 10mM.
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HM30181 mesylate salt, a tetrazole derivative, is known as a P-glycoprotein inhibitor that has inhibitory activities on multidrug resistance in cancer cells[1,5]. HM30181 has a strong inhibitory effect on MDR1-mediated paclitaxel transport in membrane vesicles. The IC50 value of HM30181 is 0.63 nM[2].
HM30181(10-10M-10-4M;5 min; 37℃) is an effective inhibitor of MDR1in 293FRT-MDR1 cells[2]. The survival inhibition rates of 0.1 nM and 1 nM Encequidar (HM30181) were 20% and 42% respectively, at 100 nM and 1000 nM NSC 125973[3].
HM30181 can significantly improve the bioavailability of oral paclitaxel. In the xenograft model in nude mice, oral co-administration of paclitaxel and HM30181 effectively inhibited tumor growth [2,4].
References:
[1]. Bauer F, Wanek T, et,al. Interaction of HM30181 with P-glycoprotein at the murine blood-brain barrier assessed with positron emission tomography. Eur J Pharmacol. 2012 Dec 5;696(1-3):18-27. doi: 10.1016/j.ejphar.2012.09.013. Epub 2012 Sep 26. PMID: 23022332; PMCID: PMC3690544.
[2]. J.O. Kwak, S.H. Lee, et,al. Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel
[3]. Joo KM, Song SY, et,al.Response of brain specific microenvironment to P-glycoprotein inhibitor: an important factor determining therapeutic effect of P-glycoprotein inhibitor on brain metastatic tumors. Int J Oncol. 2008 Oct;33(4):705-12. PMID: 18813783.
[4]. Kim JC, Kim KS, et,al. Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor. Int J Pharm. 2016 Jun 15;506(1-2):93-101. doi: 10.1016/j.ijpharm.2016.04.034. Epub 2016 Apr 19. PMID: 27106527.
[5]. J.O. Lee, Y.S. Youn, et,al. Development of poly(lactic-co-glycolic acid) microparticles with pH-sensitive drug release behaviors. J. Pharm. Invest., 45 (2) (2015), pp. 151-156
| Cell experiment [1]: | |
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Cell lines |
293FRT-MDR1 cells |
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Preparation Method |
The inhibitory activities of HM30181 were measured using the ATPase assay kit. The purified membrane vesicles were diluted to 0.1 µg/µL with assay mix and a 40-µL volume of diluted membrane suspension was loaded into each well of a 96-well microplate. One µL of the tested compound dissolved in dimethylsulfoxide (DMSO) with or without Na-orthovanadate (600 mM) was added to the membrane suspension. The same volume of DMSO was added to the control wells. The mixtures were pre-incubated at 37¡栦or 10 min and the reaction was started by addition of 10 µL Mg-ATP (200 mM). After a 10-min incubation at 37¡欠the inorganic phosphate (Pi) released was determined colorimetrically. The absorbance at 600 nm was read in a microplate reader, and the concentration of liberated Pi was calculated from the calibration curve. |
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Reaction Conditions |
10-10M-10-4M;5 min; 37℃ |
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Applications |
HM30181 has a strong inhibitory effect on MDR1-mediated paclitaxel transport in membrane vesicles. The IC50 value of HM30181 is 0.63 nM. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague Dawley rats aged 8 weeks |
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Preparation Method |
Rats were housed under standard husbandry conditions. Rat plasma samples were collected after oral (p.o.) administration of paclitaxel with or without HM30181. |
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Dosage form |
10mg/kg; p.o;0-25hr |
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Applications |
HM30181 can significantly improve the bioavailability of oral paclitaxel. |
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References: [1]. J.O. Kwak, S.H. Lee, et,al. Selective inhibition of MDR1 (ABCB1) by HM30181 increases oral bioavailability and therapeutic efficacy of paclitaxel |
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| Cas No. | 849675-87-2 | SDF | |
| 别名 | HM30181 mesylate; HM30181A mesylate | ||
| Canonical SMILES | O=C(C1=CC(C2=CC=CC=C2O1)=O)NC3=CC(OC)=C(OC)C=C3C4=NN(C5=CC=C(CCN6CC7=C(C=C(OC)C(OC)=C7)CC6)C=C5)N=N4.CS(=O)(O)=O | ||
| 分子式 | C39H40N6O10S | 分子量 | 784.83 |
| 溶解度 | DMSO : 25 mg/mL (31.85 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.2742 mL | 6.3708 mL | 12.7416 mL |
| 5 mM | 0.2548 mL | 1.2742 mL | 2.5483 mL |
| 10 mM | 0.1274 mL | 0.6371 mL | 1.2742 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet