Lumacaftor

SKU: orb1305285

Description

Lumacaftor (VRT 826809) is a small molecule corrector that facilitates the proper folding and cellular trafficking of the F508del-CFTR protein, with an EC50 of 100 nM in FRT cells. It is a key research tool for studying cystic fibrosis mechanisms in vitro and has been evaluated in preclinical in vivo models to assess CFTR correction and function.

Research Area

Cell Biology, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 936727-05-8
• MW: 452.41
• Purity: 99.72%
• Formula: C₂₄H₁₈F₂N₂O₅
• SMILES: Cc1ccc(NC(=O)C2(CC2)c2ccc3OC(F)(F)Oc3c2)nc1-c1cccc(c1)C(O)=O
• Target: CFTR,Autophagy
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:6 mg/mL (13.26 mM);DMSO:247 mg/mL (545.96 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (11.05 mM)

Bioactivity

• Target IC50:
  F508del CFTR:0.1 μM (EC50, Fischer rat thyroid cells)
• In Vitro:
  In cultured human bronchial epithelial cells isolated from patients with CF homozygous for F508del, Lumacaftor (VX-809) improved F508del-CFTR processing in the endoplasmic reticulum and enhanced chloride secretion to approximately 14% of non-CF human bronchial epithelial cells (EC50: 81 nM), a level associated with mild CF in patients with less disruptive CFTR mutations . VX-809 produced a concentration-dependent increase in the HRP luminescence signal after incubation with cells at 37°C or 27°C in both cell lines, with a similar EC50 value of approximately 0.3 μM .
• Cell Research:
  FRT, HEK-293, or HBE cells expressing CFTR or F508del-CFTR were incubated for 24 h at 37 °C with or without VX-809 in the assay media. After incubation, cells were harvested in ice-cold D-PBS solution (without calcium and magnesium) and pelleted at 1,000 × g at 4 °C. Cell pellets were lysed in 1% Nonidet P-40, 0.5% sodium deoxycholate, 200 mM NaCl, 10 mM Tris, pH 7.8, and 1 mM EDTA plus protease inhibitor mixture (1:250) for 30 min on ice. Lysates were spun for 10 min at 10,000 × g at 4 °C to pellet nuclei and insoluble material. Approximately 12 μg total protein was heated in Laemmli buffer with 5% β-mercaptoethanol at 37 °C for 5 min and loaded onto a 3% to 8% Tris-acetate gel. The gel was transferred to nitrocellulose and processed for Western blotting by using monoclonal CFTR antibody 769 or polyclonal to GAPDH. Blots were developed by enhanced chemiluminescence. Quantification of the relative amounts of bands C and GAPDH was performed by using NIH ImageJ analysis of scanned films .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

VX809, VX-809, VRT 826809, VRT826809, VRT-826809, VX 809, inhibit, Lumacaftor, Inhibitor, F508del-CFTR, Cystic fibrosis transmembrane conductance regulator, CFTR, Autophagy

Compound Identifiers

PubChem CID

16678941