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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。 |
靶点 |
|
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 37C 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]. |
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 |
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 |
|
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 << |
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 |
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 |