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鲁玛卡托 /Lumacaftor {[allProObj[0].p_purity_real_show]}

货号:A121674 同义名: VX-809;VRT 826809

Lumacaftor (VX-809; VRT 826809) 是一种CFTR调节剂,可纠正CFTR蛋白的折叠和运输。

Lumacaftor 化学结构 CAS号:936727-05-8
Lumacaftor 化学结构
CAS号:936727-05-8
Lumacaftor 3D分子结构
CAS号:936727-05-8
Lumacaftor 化学结构 CAS号:936727-05-8
Lumacaftor 3D分子结构 CAS号:936727-05-8
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Lumacaftor 纯度/质量文件 产品仅供科研

货号:A121674 标准纯度: {[allProObj[0].p_purity_real_show]}
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产品名称 CFTR 其他靶点 纯度
Ataluren 98%
Lumacaftor ++++

F508del-CFTR, EC50: 0.1 μM

98%
CFTR(inh)-172 +++

CFTR, Ki: 300 nM

99%+
GlyH-101 +

CFTR, Ki: 4.3 μM

99%+
IOWH-032 ++

CFTR, IC50: 1.01 μM

99%+
Tezacaftor 99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Lumacaftor 生物活性

靶点
  • CFTR

    F508del-CFTR, EC50:0.1 μM

描述 Cystic fibrosis (CF) is a genetic disorder with the loss of chloride transport due to the defects in CF transmembrane conductance regulator (CFTR) protein. VX-809 is a CFTP corrector that partially increases the delivery of CFTR to cell surface, thereby restoring the function of chloride transportation. It improved the maturation of F508del-CFTR, the most common CFTR mutation, in FRT cells with an EC50 value at 0.1 μM; and increased F508del-CFTR-mediated chloride transport with an EC50 at 0.5 μM. Data from F508del-HEK293 cells showed that incubation with 3 μM VX-809 for 24 hours increased F508del-CFTR exit from the endoplasmic reticulum by 6 folds compared with control cells. Also, cultured F508del-HBE cells treated with 3 μM VX-809 for 48 hours showed 14% higher maximal level of chloride transport compared to normal HBE cells[5]. In a human lung epithelium-derived cell line that was transfected with horseradish peroxidase (HRP)-tagged CFTR (F508-HRP CFBE41o-), cells treated with 2 μM VX-809 at 37C for 24 hours showed 4-fold HRP luminescence signal increase compared to DMSO-treated cells. Similar result was also found in R1070W-HRP CFBE41o- cells with 2.5-fold signal increase after VX-809 treatment at the concentration of 2 μM[6]. A phase 2 study in homozygous CF patients reported that daily intake of 100 and 200 mg VX-809 for 28 days significantly decreased their elevated sweat chloride values[7].
作用机制 VX-809 suppresses the folding defects of transmembrane conductance regulator (CFTR) protein by stabilizing an N-terminal domain in the CFTR that contains membrane-spanning domain 1[8].

Lumacaftor 细胞研究

细胞系 浓度 检测类型 检测时间 活动说明 数据源
human CFBE41o cells Function assay Corrector activity at CFTR F508del mutant (unknown origin) expressed in human CFBE41o cells assessed as increase in fully glycosylated protein by western blot analysis 26041577

Lumacaftor 动物研究

Dose Mice: 1.5 mg/kg[3] (i.v.) Rat: 1 mg/kg[4] (p.o.), 1 mg/kg - 600 mg/kg[3] (p.o.), 1 mg/kg - 5 mg/kg[3] (i.v.)
Administration i.v., p.o.
Pharmacokinetics
Animal Rats[3]
Dose 30 mg/kg (p.o.)
3 mg/kg (i.v.)
Administration p.o.
i.v.
F 69.7% (p.o.)
T1/2 6.46 h (p.o.)
8.62 h (i.v.)
Tmax 2.0 h (p.o.)
0.083 h (i.v.)
Cmax 66200 ng/g (p.o.)
24600 ng/g (i.v.)
AUC0→∞ 410000 ng·h/g (p.o.)
58900 ng·h/g (i.v.)
AUC0→t 410000 ng·h/g (p.o.)
58900 ng·h/g (i.v.)

Lumacaftor 临床研究

NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03474042 Cystic Fibrosis Phase 2 Completed - Germany ... 展开 >> Study Site II Berlin, Germany Study Site X Dresden, Germany Study Site III Essen, Germany Study Site IV Frankfurt, Germany Study Site I Heidelberg, Germany Study Site V Köln, Germany Study Site VI München, Germany Study Site IX Stuttgart, Germany Study Site VIII Tübingen, Germany 收起 <<
NCT02821130 - Active, not recruiting December 2019 Canada, British Columbia ... 展开 >> UBC James Hogg Research Centre, St. Paul's Hospital Vancouver, British Columbia, Canada, V6Z1Y6 收起 <<
NCT02965326 Cystic Fibrosis Not Applicable Recruiting October 2020 France ... 展开 >> Necker Hospital Recruiting Paris, France, 75014 Contact: SERMET Isabelle, Professor    01 44 49 48 87    isabelle.sermet@nck.aphp.fr    Principal Investigator: SERMET Isabelle, Professor 收起 <<

Lumacaftor 参考文献

[1]lumacaftor

[2]Van Goor F, Hadida S, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18843-8.

[3]108(46):18843-8.

[4]86(1):42-51.

[5]Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, Decker CJ, Miller M, McCartney J, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu PA. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18843-8.

[6]Phuan PW, Veit G, Tan J, Roldan A, Finkbeiner WE, Lukacs GL, Verkman AS. Synergy-based small-molecule screen using a human lung epithelial cell line yields ΔF508-CFTR correctors that augment VX-809 maximal efficacy. Mol Pharmacol. 2014 Jul;86(1):42-51.

Lumacaftor 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.21mL

0.44mL

0.22mL

11.05mL

2.21mL

1.11mL

22.10mL

4.42mL

2.21mL

Lumacaftor 技术信息

CAS号936727-05-8
分子式C24H18F2N2O5
分子量 452.41
别名 VX-809;VRT 826809;Orkambi;​Lumacaftor
运输蓝冰
存储条件

液体 -20°C:3-6个月-80°C:12个月

粉末 Keep in dark place,Inert atmosphere,Room temperature

溶解度

DMSO: 25 mg/mL(55.26 mM),配合低频超声,并水浴加热至45℃助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方

IP 2% DMSO+2% Tween80+40% PEG300+water 4 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

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