5.30541

CFTR Potentiator, VX-770

• 別名: 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
• 実験式（ヒル表記法）: C₂₄H₂₈N₂O₃
• CAS番号: 873054-44-5
• 分子量: 392.49
• MDL番号: MFCD17171361
• UNSPSCコード: 51111800
• NACRES: NA.77

特性

• アッセイ: ≥98% (HPLC)
• 品質水準: 100
• フォーム: powder
• メーカー／製品名: Calbiochem^®
• 保管条件: OK to freeze; protect from light
• 色: off-white
• 溶解性: DMSO: 100 mg/mL
• 保管温度: 2-8°C
• SMILES記法: [nH]1c2c([c](c(c1)C(=O)Nc3c(cc(c(c3)O)C(C)(C)C)C(C)(C)C)=O)cccc2
• 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 Key: PURKAOJPTOLRMP-UHFFFAOYSA-N

詳細

詳細

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.

生物化学的／生理学的作用

Cell permeable: yes

Primary Target
WT and G551D mutant forms of cell surface CFTR

Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

再構成

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

その他情報

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.

法的情報

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

安全性情報

• 保管分類コード: 11 - Combustible Solids
• WGK: WGK 3
• 引火点(°F): Not applicable
• 引火点(℃): Not applicable