5.30541

CFTR Potentiator, VX-770

• 同義詞: CFTR Potentiator, VX-770, N-(5-Hydroxy-2,4- bis(2-methyl-2-propanyl)phenyl]-4-oxo-1,4-dihydro-3-quinolinecarboxamide, Cystic Fibrosis Transmembrane Conductance Regulator Potentiator, VX 770, Ivacaftor, Kalydeco, N-(5-Hydroxy-2,4-bis(2-methyl-2-propanyl)phenyl]-4-oxo-1,4-dihydro-3-quinolinecarboxamide, Cystic Fibrosis Transmembrane Conductance Regulator Potentiator, VX 770, Ivacaftor, Kalydeco
• 經驗公式（希爾表示法）: C₂₄H₂₈N₂O₃
• CAS號碼: 873054-44-5
• 分子量：: 392.49
• 分類程式碼代碼: 51111800
• NACRES: NA.77

屬性

• 化驗: ≥98% (HPLC)
• 品質等級: 100
• 形狀: powder
• 製造商／商標名: Calbiochem^®
• 儲存條件: OK to freeze; protect from light
• 顏色: off-white
• 溶解度: DMSO: 100 mg/mL
• 儲存溫度: 2-8°C
• InChI: 1S/C24H28N2O3/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28/h7-13,27H,1-6H3,(H,25,28)(H,26,29)
• InChI 密鑰: PURKAOJPTOLRMP-UHFFFAOYSA-N

描述

一般說明

A cell-permeable, orally bioavailable dihydroquinoline-carboxamide compound that acts as a potentiator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by directly binding to WT and G551D mutant forms in an allosteric and reversible manner (~ 10 µM) and increases the open probability to restore lung function. Enhances cAMP/PKA-signaling mediated gating activity of both WT and G551D mutants and its potentiation activity is dependent upon the phosphorylated status of CFTR. Does not compete for binding to the canonical ATP-binding catalytic site; but the rate of flux through CFTR increase by 1.5 to 2 fold when ATP concentrations are increased. Shown to increase Cl^- secretion by about 10 fold in cultured human CF bronchial epethelia (HBE) carrying G551D/F508del mutations and increases forskolin-stimulated transepethial current (IT; EC₅₀ = 236 nM) far more effectively than genistein (EC₅₀ = 16 µM). Displays favorable pharmacokinetic properties with t_1/2= 12 h.

A cell-permeable, orally bioavailable dihydroquinoline-carboxamide compound that acts as a potentiator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by directly binding to WT and G551D mutant forms in an allosteric and reversible manner (~ 10 µM) and increases the open probability to restore lung function. Enhances cAMP/PKA-signaling mediated gating activity of both WT and G551D mutants and its potentiation activity is dependent upon the phosphorylated status of CFTR. Does not compete for binding to the canonical ATP-binding catalytic site; but the rate of flux through CFTR increase by 1.5 to 2 fold when ATP concentrations are increased. Shown to increase Cl^- secretion by about 10 fold in cultured human CF bronchial epethelia (HBE) carrying G551D/F508del mutations and increases forskolin-stimulated transepethial current (IT; EC₅₀ = 236 nM) far more effectively than genistein (EC₅₀ = 16 µM). Displays favorable pharmacokinetic properties with t_1/2= 12 h.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

生化／生理作用

Cell permeable: yes

Primary Target
WT and G551D mutant forms of cell surface CFTR

Reversible: yes

包裝

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重構

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

其他說明

Namkung, W., et al. 2013. Mol. Pharmacol.84, 384.
Eckford, P.D.W., et al. 2012. J. Biol. Chem.287, 36639.

Van Goor, F., et al 2009. Proc. Natl. Acad. Sci. USA106, 18825.

法律資訊

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

安全資訊

• 儲存類別代碼: 11 - Combustible Solids
• 水污染物質分類（WGK）: WGK 3
• 閃點（°F）: Not applicable
• 閃點（°C）: Not applicable