VX-661
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
VX-661是一种vertex衍生物,可校正F508del-CFTR转运,并可在体外增加F508del-CFTR蛋白的活性[1]。
VX-661单独使用或与ivacaftor联合使用可增加F508del-CFTR向细胞表面的转运。VX-661目前处于2期临床研究[1]。
参考文献:
[1] S. Donaldson, J. Pilewski, M. Griese, Q. Dong, P.-S. Lee, for the VX11–661-101 Study Group. WS7.3 VX-661, an investigational CFTR corrector, in combination with ivacaftor, a CFTR potentiator, in patients with CF and homozygous for the F508Del-CFTR mutation: Interim analysis. Journal of Cystic Fibrosis, Volume 12, Supplement 1, June 2013, Page S14
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 520.5 |
Cas No. | 1152311-62-0 |
Formula | C26H27F3N2O6 |
Solubility | ≥21.8 mg/mL in DMSO; insoluble in EtOH; ≥24.3 mg/mL in H2O |
Chemical Name | 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-[1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide |
SDF | Download SDF |
Canonical SMILES | CC(C)(CO)C1=CC2=CC(=C(C=C2N1CC(CO)O)F)NC(=O)C3(CC3)C4=CC5=C(C=C4)OC(O5)(F)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1]: | |
细胞系 |
人源囊性纤维化支气管上皮细胞系CFBE41o |
溶解方法 |
在DMSO中的溶解度>21.8mg/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 |
3 μM, 24 hours, 26°C. |
应用 |
VX-661可以部分恢复错误折叠和加工的ΔF508-CFTR(囊性纤维化跨膜传导调节因子),恢复其质膜密度。VX-770可以增强通道门控和电导。VX-770会减弱VX-661的修正效率,而VX-661也会减弱VX-770效率(可能是由于成熟的ΔF508-CFTR池的部分稳定)。在非囊性纤维化的人源支气管上皮细胞中,慢性给药VX-661,急性给药VX-770,与cAMP激动剂的联合使用可以使ΔF508-CFTR的电导率提高至约25%。 |
临床实验 [2]: | |
疾病模型 |
囊性纤维化病人(带有F508del纯合子或杂合子突变) |
剂量 |
10、30、100或150 mg每日口服,连续28天。 |
应用 |
在VX-661单独使用组和与VX-770连用组中,中期检测结果发现汗中氯化物含量降低。在28天时,相比于安慰剂组,VX-661 100 mg ,150 mg分别与VX-770一起使用时,病人的FEV1(1秒强制呼气量) 变化显著,分别在9%和7.5%的病人中有显著结果。 |
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] S. Donaldson, J. Pilewski, M. Griese, Q. Dong, P.-S. Lee, for the VX11–661-101 Study Group. WS7.3 VX-661, an investigational CFTR corrector, in combination with ivacaftor, a CFTR potentiator, in patients with CF and homozygous for the F508Del-CFTR mutation: Interim analysis. Journal of Cystic Fibrosis, Volume 12, Supplement 1, June 2013, Page S14 [2] National Institutes of Health. Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation (February 1, 2012). Available at: http://clinicaltrials.gov/ct2/show/NCT01531673. Accessed May 5, 2015. |
Description | VX-661是F508 del CFTR的第二个校正子。 | |||||
靶点 | F508 del CFTR | |||||
IC50 |
质量控制和MSDS
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