Cat No:LP000219
Product Name:vx809
CAS No:936727-05-8
Purity: ≥99%
Solubility: In DMSO
Storage: -10°C
In fischer rat thyroid (FRT) cells, VX-809 improves F508del-CFTR maturation by 7.1±0.3 fold (n=3) compared with vehicle-treated cells (EC50, 0.1±0.1 μM; n=3) and enhances F508del-CFTR-mediated chloride transport by approximately fivefold (EC50, 0.5±0.1 μM; n=3). At VX-809 concentrations greater than 10 μM, the response is reduced, resulting in a bell-shaped dose-response relationship with an IC50 of approximately 100 μM. VX-809 is orally bioavailable in rats and achieved in vivo plasma levels significantly above concentrations required for in vitro efficacy[1]. VX-809 produces 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. In F508-HRP CFBE41o- cells at 37°C, VX-809 increases the signal maximally to approximately 250 luminescence arbitrary units (a.u.) over the DMSO control baseline of approximately 60 a.u., representing an approximately 4-fold signal increase. Similarly, with the R1070W-HRP CFBE41o- cells, VX-809 increases the signal maximally to approximately 220 a.u. over the DMSO control baseline of approximately 85 a.u., representing an approximately 2.5-fold signal increase. Therefore, both cell lines produced robust signals with a good dynamic range for high-throughput screening[2].
Oral dosing of 1 mg/kg VX-809 in male Sprague-Dawley rats results in a Cmax of 2.4±1.3 μM with a t1/2 of 7.7±0.4 h (mean±SD; n=3), indicating that that VX-809 is orally bioavailable and able to reach plasma levels that significantly exceeded EC50s for F508del-CFTR correction[1].
