| Description | GW1929 is a potent PPAR-γ agonist (pKi: 8.84 for human PPAR-γ; pEC50s of 8.56 and 8.27 for human and murine PPAR-γ). |
| In vitro | GW1929是一种强效的PPAR-γ激活剂，对人类和小鼠的PPAR-γ的pEC50分别为8.56和8.27，同时对人类PPAR-γ、PPAR-α和PPAR-δ的pKis分别为8.84、小于5.5和小于6.5[1]。在浓度为10μM时，GW1929能够抑制TBBPA诱导的新皮层细胞培养中caspase-3的增加和TBBPA刺激的LDH释放[2]。 |
| In vivo | GW1929（0.5、1、5 mg/kg，p.o.）在治疗14天后显著降低了Zucker糖尿病肥胖（ZDF）大鼠的非空腹血糖水平，并具有抗脂解作用。在ZDF大鼠中，GW1929（1、5 mg/kg，p.o.）增强了β细胞对葡萄糖刺激的胰岛素分泌能力[1]。 |
| Cell experiments | For the experiments, the cells are plated in 96-well plates at a density of 2 × 10^5 cells per cm2 and cultured in the presence of TBBPA, in concentrations ranging from 1 nM to 100 μM TBBPA. TBBPA is dissolved in DMSO, resulting in a final vehicle concentration of 0.1 % (v/v). Control (no vehicle) and DMSO-treated wells are included in the experimental design to determine the effect of DMSO. To study whether PPAR-γ is involved in the neurotoxic effect of TBBPA, cells are co-treated with 10 μM TBBPA and 10 μM GW1929 or GW9662. After 6 or 24 h of culture, 100 μL medium is collected for the LDH analysis, and the cells are collected and frozen at ?70°C for the caspase-3 activity measurements [2]. |
| Animal experiments | Animals are housed at 72°F and 50% relative humidity with a 12-h light and dark cycle and fed Formulab Diet 5008. Age- (60-day) and glucose-matched male Zucker diabetic fatty rats are gavaged twice daily for 14 days with vehicle (0.05 M N-methylglucamine), GW1929 (0.5, 1.0, or 5.0 mg/kg), or troglitazone (as the milled extrudate, in a suspension in methylcellulose, 50, 150, and 500 mg/kg). Another group of animals receives a mixture of Humulin N and Humulin R by subcutaneous injection twice daily. On days 7 and 14 of dosing, nonfasted measurements of glucose, lactate, insulin, total cholesterol, TGs, F FAs, and hematocrit are obtained. On day 14 of dosing, samples for serum drug levels (2-h postdose) and glycosylated hemoglobin measurements are also collected. In addition, once weekly, three animals from each group are placed in metabolic chambers for 48 h for quantitation of 24-h food and water consumption. Body weights are recorded throughout the study. At the conclusion of the study, perfused pancreas experiments are performed on 12 animals (n = 4 per group) that have received either GW1929 (1 and 5 mg/kg) or vehicle, to directly evaluate the effects of treatment on basal and glucose-stimulated insulin secretion. The remaining animals are killed, and their pancreases are processed for immunocytochemistry [1]. |
| Target activity | PPARγ (human):8.84 (pKi) |
| molecular weight | 495.57 |
| Molecular formula | C30H29N3O4 |
| CAS | 196808-24-9 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 33 mg/mL (66.59 mM) |
| References | 1. Brown KK, et al. A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes. 1999 Jul;48(7):1415-24. 2. Wojtowicz AK, et al. PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells. Neurotox Res. 2014 Apr;25(3):311-22. |