GSK3787 is a selective and irreversible peroxisome proliferator-activated receptor δ (PPARδ) antagonist with pIC₅₀ of 6.6.

GSK3787 is identified as a potent and selective hPPARδ ligand (pIC₅₀=6.6) with no measurable affinity for hPPARα or hPPARγ (pIC₅₀ < 5) in our standard in vitro ligand displacement assay. GSK3787 is inactive against hPPARα and hPPARγ in similar functional antagonist assays. GSK3787 fails to activate the receptor in a standard hPPARδ-GAL4 chimera cell-based reporter assay. GSK3787 is a selective PPARδ antagonist with equipotent species activity against the human and mouse receptor^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

GSK3787 has pharmacokinetic properties suitable for use as an in vivo PPARδ antagonist tool compound in mice. GSK3787 is administered intravenously (0.5 mg/kg) and orally (10 mg/kg) to male C57BL/6 mice. Mean clearance (CL) and volume of distribution at steady state (V_ss) following iv administration are 39±11 (mL/min)/kg and 1.7±0.4 L/kg, respectively. Following oral administration, good exposure (C_max=881±166 ng/mL, AUC_inf=3343±332 h•ng/mL), half-life (2.7±1.1 h), and bioavailability (F=77±17%) are observed^[1]. Oral administration of GSK3787 (10 mg/kg) leads to a serum C_max of 2.2±0.4 μM in C57BL/6 male mice. Oral administration of GW0742 causes an increase in expression of Angptl4 and Adrp mRNA (known PPARβ/δ target genes) in wild-type mouse colon epithelium, and this effect is not found in Pparβ/δ-null mouse colon epithelium. Coadministration of GSK3787 with GW0742 effectively prevents the ligand-induced expression of both Angptl4 and Adrp mRNA in wild-type mouse colon epithelium, and this effect is not found in Pparβ/δ-null mouse colon epithelium. Oral administration of GSK3787 causes a modest increase in promoter occupancy of PPARβ/δ in the PPRE region of both the Angptl4 and Adrp genes, but coadministration of GSK3787 with GW0742 results in markedly less accumulation of PPARβ/δ in the PPRE region of both the Angptl4 and Adrp genes in wild-type mouse colon epithelium^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

392.78

C₁₅H₁₂ClF₃N₂O₃S

188591-46-0

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 50 mg/mL (127.30 mM)

* “≥” means soluble, but saturation unknown.

*

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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

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: 2.5 mg/mL (6.36 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (6.36 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 25.0 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: ≥ 2.5 mg/mL (6.36 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.36 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Shearer BG, et al. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 2010 Feb 25;53(4):1857-61.

  [2]. Palkar PS, et al. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787. Mol Pharmacol. 2010 Sep;78(3):419-30.

Mice^[2]
For RNA and DNA analysis, male wild-type and Pparβ/δ-null mice are administered vehicle (corn oil), GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or GW0742 and GSK3787 by oral gavage 3 h before euthanasia. After euthanasia, colons are carefully dissected. To isolate colon epithelium, colons are flushed with phosphate-buffered saline, and epithelial cells are scraped from mucosa using a razor blade. The isolated tissues are used for RNA isolation. For glucose-tolerance tests, male wild-type and Pparβ/δ-null mice are administered vehicle (corn oil), GW0742 (10 mg/kg), GSK3787 (10 mg/kg), or Rosiglitazone (20 mg/kg) by oral gavage once a day for 2 weeks.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Shearer BG, et al. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 2010 Feb 25;53(4):1857-61.

  [2]. Palkar PS, et al. Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787. Mol Pharmacol. 2010 Sep;78(3):419-30.