产品说明
一般描述
A non-cytotoxic (30 µM for 48 h in human airway epithelial Calu-3 cultures) aminopyrazolocarbonitrile compound that is shown to activate both wt- and ΔF508-CFTR channel activity in a cAMP-independent, reversible, and CFTRinh-172- (Cat. Nos. 219670 & 219674) blockable (IC50 & IC100 = 0.37 & 30 µM, respectively, against 30 µM Cact using Fisher rat thyroid/FRT cells with wt-CFTR) manner, without affecting CaCC (Calcium-activated chloride channel) function or cellular levels of Ca2+ and cAMP. The maximum activation inducible by Cact-A1 (ECmax = 13 to 30 µM in Cl- current induction using in Fisher rat thyroid/FRT and primary human bronchial epithelial/HBE cells) is comparable to that achievable via cAMP stimulation by Forskolin treatment (ECmax = 20 µM; Cat. Nos. 344270 & 34427082), which cannot be further enhanced by Forskolin co-treatment in cells expressing wt-CFTR, although additive effects are seen when Cact-A1 and Forskoklin are applied at suboptimal concentrations to cells with wt-CFTR or when the two drugs are applied at respective ECmax to cells with surface ΔF508-CFTR. Neither Cact-A1 nor Forskolin alone (at 30 µM; and 20 µM;, respectively) can effectively activate FRT with surface G551D-CFTR or primary HNPE (human nasal polyp epithelial) cells with surface G551D/Y1092X-CFTR, while Cact-A1-Forskolin co-treatment results in synergistic activation and maximally achievable activation is reported with a three-drug co-treatment using Cact-A1, Forskolin, and VX-770 (at 30, 20, and 10 µM, respectively).
A cell-permeable, non-toxic aminopyrazolocarbonitrile compound that acts as a potent, selective, reversible and cAMP-independent activator of CFTR-dependent Cl- channel in airway epithelial cells (EC50 = 1.6 µM in CFTR-expressing Fisher rat thyroid cells). Also shown to activate ΔF508-CFTR in primary CF-HBE cell cultures (EC50 = 3.5 µM). Reported to directly bind to the same site as CFTRinh-172 (>Cat. No. 219670, >Cat. No. 219674). Does neither elevate intracellular cAMP levels nor appear to have any requirement for cAMP agonist, such as forskolin (Cat. No. 344270, Cat. No. 344282). Shown to additively potentiate the G551D-CFTR Cl- current activated by forskolin with CFTR potentiator, VX-770. Exerts no effect on either Ca2+-activated Cl- channel (TMEM16A) or intracellular Ca2+ levels.
生化/生理作用
Cell permeable: yes
Reversible: yes
Primary Target
CFTR
包装
Packaged under inert gas
警告
Toxicity: Standard Handling (A)
重悬
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
其他说明
Namkung, W., et al. 2013. Mol. Pharmacol.84, 384.
法律信息
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
基本信息
经验(实验)分子式 | C16H13N5O |
分子量 | 291.31 |
产品性质
质量水平 | 100 |
测定 | ≥98% (HPLC) |
形式 | powder |
manufacturer/tradename | Calbiochem® |
储存条件 | OK to freeze protect from light |
颜色 | light yellow |
溶解性 | DMSO: 100 mg/mL |
储存温度 | 2-8℃ |
安全信息
储存分类代码 | 11 - Combustible Solids |
WGK | WGK 3 |
闪点(F) | Not applicable |
闪点(C) | Not applicable |
Sigma-Aldrich