GW6471 is a potentPPARαantagonist.

In a cell-based reporter assay, GW6471 completely inhibits GW409544-induced activation of PPARα with an IC₅₀of 0.24 μM^[1]. The functional role of PPARα is evaluated on renal cell carcinoma (RCC) cell viability by MTT assay. Both Caki-1 (VHL wild type) and 786-O (VHL mutated) cells are incubated separately with a specific PPARα agonist, WY14,643, or a specific PPARα antagonist, GW6471 at concentrations from 12.5 to 100 μM for 72 hours, and cell viability is assessed. While WY14,643 either has no affect on, or slightly increased, cell viability, GW6471 significantly and dose-dependently inhibits cell viability (up to approximately 80%) in both cell lines^[2].

To test the antitumor activity of PPARα antagonism in vivo, a subcutaneous xenograft mouse model is used. Caki-1 cells are implanted subcutaneously in nude (Nu/Nu) mice. After tumor masses reach ~5 mm in diameter, GW6471 is administrated intraperitoneally every other day for 4 wk at a dose (20 mg/kg mouse body wt) that is described to be effective in an in vivo dose-response study and confirmed here to be efficacious. There are significant differences in tumor growth between vehicle- and GW6471-treated animals. No toxicity is observed at the doses of GW6471 based on weights of the animals, and laboratory values, including kidney and liver function tests, are not adversely affected. To demonstrate on-target effects of GW6471, c-Myc levels are evaluated in the tumors, which show significant decreases in the GW6471-treated animals^[3].

619.67

Solid

C₃₅H₃₆F₃N₃O₄

880635-03-0

Room temperature in continental US; may vary elsewhere.

DMSO : 83.33 mg/mL(134.47 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: ≥ 2.08 mg/mL (3.36 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.36 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 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% (20%SBE-β-CDin saline)

  Solubility: 2.08 mg/mL (3.36 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.08 mg/mL (3.36 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.08 mg/mL (3.36 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (3.36 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。