VX-661
(Synonyms: VX-661) 目录号 : GC14920
An investigational compound that promotes the maturation of delta F508 CFTR
Cas No.:1152311-62-0
Sample solution is provided at 25 µL, 10mM.
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VX-661, one of vertex derivatives, corrects F508del-CFTR trafficking and increases F508del-CFTR protein activity in vitro [1].
VX-661 treated alone or in combination with ivacaftor have shown to enhance F508del-CFTR trafficking to the cell surface. VX-661 has been at phase 2 study [1].
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
| Cell experiment [1]: | |
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Cell lines |
human CF bronchial epithelial cell line CFBE41o |
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Preparation method |
The solubility of this compound in DMSO ＞21.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
3 μM for 24 hours at 26°C. |
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Applications |
VX-661 could partially revert the folding and processing defects and rescue PM(plasma membrane) densities of ΔF508-CFTR(Cystic fibrosis transmembrane regulator). VX-770 was a potentiators that increase channel gating and conductance.VX-770 reduced the correction efficacy of corrector VX-661. The VX-770 effect was attenuated in VX-661 treated cells, probably due to partial stabilization of the mature ΔF508-CFTR pool. A combination of chronic VX-661 and acute VX-770, together with a cAMP (cyclic adenosine 3′,5′-monophosphate) agonist, increased ΔF508-CFTR conductance to ~25% of that in non-CF HBE (human bronchial epithelial). |
| Clinical experiment [2]: | |
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Disease models |
CF (Cystic fibrosis) patients who were homozygous or heterozygous for the F508del mutation. |
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Dosage form |
10,30, 100, or 150 mg daily in oral for 28 days |
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Application |
Interim results found decreases in sweat chloride with VX-661 alone and in combination with ivacaftor(VX-770). A relative change in FEV1 (forced expiratory volume in one second) compared with placebo was significant at 28 days with VX-661 100 mg (9%) and 150 mg (7.5%) in combination with ivacaftor. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. |
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| Cas No. | 1152311-62-0 | SDF | |
| 别名 | VX-661 | ||
| 化学名 | 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 | ||
| 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 | ||
| 分子式 | C26H27F3N2O6 | 分子量 | 520.5 |
| 溶解度 | ≥ 21.8mg/mL in DMSO | 储存条件 | Store at -20°C , stored under nitrogen |
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9212 mL | 9.6061 mL | 19.2123 mL |
| 5 mM | 0.3842 mL | 1.9212 mL | 3.8425 mL |
| 10 mM | 0.1921 mL | 0.9606 mL | 1.9212 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