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Elacridar

现货
Catalog No.
A3384
BCRP抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 750.00
现货
10mg
¥ 650.00
现货
20mg
¥ 2,310.00
现货
50mg
¥ 2,100.00
现货
100mg
¥ 3,150.00
现货

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Background

Elacridar is a potent inhibitor of P-glycoprotein with IC50 values of 193 nM. [1]

P-glycoprotein (permeability glycoprotein) is an important membrane protein. It pumps many foreign substances out of cells. P-glycoprotein belongs to the MDR/TAP subfamily. P-glycoprotein is transmembrane glycoprotein which is about 170 kDa. It is expressed in certain cell types primarily in the pancreas, liver, colon and kidney. It contains 6 transmembrane domains in the N-terminal half of the molecule. It also contains an ATP-binding site in the large cytoplasmic domain. P-glycoprotein binds to the substrate at the cytoplasmic side of the protein. When ATP binds to the cytoplasmic side, the substrate was excreted from the cell. P-glycoprotein can pump toxins or drugs back into the intestinal lumen, pumps them into bile ducts in liver cells.In some cancer cells, P-glycoprotein is overexpressed. It is involved in multidrug resistance of cancer cells.[2]

Elacridar can significantly inhibit the activity of P-glycoprotein at 1μM in MDCKII cells which overexpress P-glycoprotein.[3] In the parental MDCK-II cells, elacridar at 5μM completely inhibit the polarized sunitinib transport.[4] Elacridar did not inhibit the activity of several human cytochromeP450 enzymes in vitro. The absolute bioavailability was about 0.47 and 1.3 respectively, when elacridar was given in the orally and microemulsion, intraperitoneally at 10 mg/kg in mice.[3] Elacridar also can significantly increase sunitinib brain accumulation levels in mice at 10 mg/kg.[4]

References:
[1].  Bankstahl JP, Bankstahl M, Romermann K, Wanek T, Stanek J, Windhorst AD, Fedrowitz M, Erker T, Muller M, Loscher W et al: Tariquidar and elacridar are dose-dependently transported by P-glycoprotein and Bcrp at the blood-brain barrier: a small-animal positron emission tomography and in vitro study. Drug Metab Dispos, 41(4):754-762.
[2].  Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL et al: Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 2009, 323(5922):1718-1722.
[3].  Sane R, Mittapalli RK, Elmquist WF: Development and evaluation of a novel microemulsion formulation of elacridar to improve its bioavailability. J Pharm Sci, 102(4):1343-1354.
[4].  Tang SC, Lagas JS, Lankheet NA, Poller B, Hillebrand MJ, Rosing H, Beijnen JH, Schinkel AH: Brain accumulation of sunitinib is restricted by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration. Int J Cancer, 130(1):223-233.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt563.64
Cas No.143664-11-3
FormulaC34H33N3O5
SynonymsGF120918;GW0918;GG918;GF-120918;GF 120918
Solubility≥56.4 mg/mL in DMSO, <2.4 mg/mL in EtOH, <2.54 mg/mL in H2O
Chemical NameN-[4-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10H-acridine-4-carboxamide
SDFDownload SDF
Canonical SMILESCOC1=CC=CC2=C1NC3=C(C2=O)C=CC=C3C(=O)NC4=CC=C(C=C4)CCN5CCC6=CC(=C(C=C6C5)OC)OC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

人肾癌细胞系786-O和人乳腺癌细胞系MCF-7

溶解方法

在DMSO中的溶解度大于56.4 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

5 μM,24 h

应用

Elacridar是P-糖蛋白的抑制剂,也可抑制ABCG2。在786-O细胞中,Elacridar显著加强sunitinib诱导的细胞毒性。P-糖蛋白功能实验表明,Elacridar可抑制P-糖蛋白的活性。

动物实验[2]:

动物模型

10-14周的野生型、Abcb1a/1b-/-、32Abcg2-/-27和Abcb1a/1b/Abcg2-/-小鼠,均具有99%以上的FVB遗传背景

剂量

口服给药,100 mg/kg

应用

在野生型小鼠中,Elacridar显著增加sunitinib的脑累积(12倍),相当于sunitinib在Abcb1a/1b/Abcg2-/-小鼠中的水平。在Abcb1a/1b/Abcg2-/-小鼠中,Elacridar对sunitinib的脑浓度无显著影响。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Sato H, Siddig S, Uzu M, et al. Elacridar enhances the cytotoxic effects of sunitinib and prevents multidrug resistance in renal carcinoma cells[J]. European journal of pharmacology, 2015, 746: 258-266.

[2]. Tang S C, Lagas J S, Lankheet N A G, et al. Brain accumulation of sunitinib is restricted by P‐glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) and can be enhanced by oral elacridar and sunitinib coadministration[J]. International journal of cancer, 2012, 130(1): 223-233.

生物活性

描述 Elacridar(GF120918; GW0918)是一种P-糖蛋白抑制剂。
靶点 P-glycoprotein          
IC50            

质量控制

化学结构

Elacridar