Lumacaftor (VX-809; VRT 826809) is aCFTRmodulator that corrects the folding and trafficking ofCFTRprotein.

EC50: 0.1 μM (CFTR)^[1]

In fischer rat thyroid (FRT) cells, Lumacaftor 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 Lumacaftor concentrations greater than 10 μM, the response is reduced, resulting in a bell-shaped dose-response relationship with an IC₅₀of approximately 100 μM. Lumacaftor is orally bioavailable in rats and achieved in vivo plasma levels significantly above concentrations required for in vitro efficacy^[1]. Lumacaftor produces a concentration-dependent increase in the HRP luminescence signal after incubation with cells at 37℃ or 27℃ in both cell lines, with a similar EC₅₀value of approximately 0.3 μM. In F508-HRP CFBE41o^-cells at 37℃, Lumacaftor 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, Lumacaftor 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 Lumacaftor in male Sprague-Dawley rats results in a C_maxof 2.4±1.3 μM with a t_1/2of 7.7±0.4 h (mean±SD; n=3), indicating that that Lumacaftor is orally bioavailable and able to reach plasma levels that significantly exceeded EC₅₀s for F508del-CFTR correction^[1].

452.41

Solid

C₂₄H₁₈F₂N₂O₅

936727-05-8

鲁玛卡托

Room temperature in continental US; may vary elsewhere.

DMSO : 25 mg/mL(55.26 mM;ultrasonic and warming and heat to 60℃)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 3 mg/mL (6.63 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (6.63 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 3 mg/mL (6.63 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (6.63 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。