GW501516

A selective PPARδ-agonist with anti-obesity activity

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5mg

￥425.00

340.00

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10mg

￥687.00

550.00

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50mg

￥1687.00

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100mg

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货号: ajci14878
CAS: 317318-70-0
别名: 2-(4-((2-(4-(三氟甲基)苯基)-5-甲基噻唑-4-基)甲基硫基)-2-甲基苯氧基)乙酸,GW 1516; GSK-516
分子式: C21H18F3NO3S2
分子量: 453.5
纯度: >98%
溶解度: ≥ 18.05 mg/mL in DMSO, ≥ 44.6 mg/mL in EtOH
储存: Store at -20°C
库存: 现货

Background

GW501516 is subtype-selective small-molecule agonist of peroxisome proliferator-activated receptor δ (PPARδ) with Ki value of 1.1nM [1].

GW501516 is discovered by combinatorial chemistry and structure-based drug design to use as an ideal chemical tool to study the function of the ubiquitously expressed PPARδ. In the cell-based transfection assay, it induces expression of a GAL4-responsive reporter gene with EC50 value of 1.2nM. GW501516 shows more than 1000-fold selective for PPARδ over other subtypes. PPARδ is expressed in many tissues that contribute to cholesterol flux, and is a RXR of partner. As an agonist of PPARδ, GW501516 is found to increase the expression of ABCA1 as well as the apoA1-specific cholesterol efflux. In primate model of human metabolic disease, GW501516 increases the level of HDLc and lowers the fasting triglycerides. GW501516 also produces fewer, yet larger, LDL and VLDL particles results in a less atherogenic lipid composition. Furthermore, GW501516 partially corrects the hyperinsulinemia in primates without adverse effects on glycemic control [1, 2].

参考文献:
[1] Wei ZL, Kozikowski AP. A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta. J Org Chem. 2003 Nov 14;68(23):9116-8.
[2] Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11.

Protocol

Cell experiment:

GW 501516 is dissolved in DMSO. Cells are starved by incubation in 0.2% FCS DMEM for 9 h, then pre-incubated with GW 501516, at a final concentration of 2.5 and 5 μM, or 0.05% DMSO as control for 3 hours, followed by stimulation with 150 μM palmitate bound to 8.0% BSA for 12 h[3].

Animal experiment:

Rats: Female Sprague Dawley rats, 12 weeks of age, are allocated to a sham-operated group and 3 OVX groups; high-dose GW 501516 (OVX-GW5), low-dose GW 501516 (OVX-GW1), and a control group (OVX-CTR), respectively. Animals receive GW 501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) is assessed by dual x-ray absorptiometry at the femur, spine, and whole body[2]. Mice: Mice are randomly allocated to different groups and receive therapeutic diet and treatment. The GW 501516-containing rodent diet is made by evenly adding GW 501516 to the control diet to a final concentration of 0.04% w/w. In the control diet, 10% of the total calories are from fat (5.5% from soybean oil and 4.5% from lard)[3].

参考文献:

[1]. Wei ZL, et al. A short and efficient synthesis of the pharmacological research tool GW501516 for the peroxisome proliferator-activated receptor delta. J Org Chem. 2003 Nov 14;68(23):9116-8.
[2]. Mosti MP, et al. Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW 501516 on bone and muscle in ovariectomized rats. Endocrinology. 2014 Jun;155(6):2178-89.
[3]. Yang X, et al. GW 501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice. PLoS One. 2011;6(9):e25271.
[4]. Chen W, et al. A metabolomic study of the PPARδ agonist GW 501516 for enhancing running endurance in Kunming mice. Sci Rep. 2015 May 6;5:9884.
[5]. Ji Y, et al. PPARβ/δ Agonist GW501516 Inhibits Tumorigenicity of Undifferentiated Nasopharyngeal Carcinoma in C666-1 Cells by Promoting Apoptosis. Front Pharmacol. 2018 Jun 28;9:648.