The in vitro PPARα/γ binding and transactivation activities of seven synthetic metabolites of muraglitazar (n = 3)
Metabolite | PPARα | PPARγ | ||||
|---|---|---|---|---|---|---|
| IC50 | EC50 (μM) Intrinsic Activity | IC50 | EC50 (μM) Intrinsic Activity | |||
| μM | % | μM | % | |||
| Muraglitazar | 0.188 ± 0.073 | 0.035 ± 0.017 | 1.41 ± 0.27 | |||
| IAa = 120 ± 16% at 1 μM | 0.247 ± 0.008 | IA = 57 ± 38% at 1 μM | ||||
| 139 ± 26% at max | 107 ± 40% at max | |||||
| M1 | >15 | >25 | >15 | >20 | ||
| M5 | >15 | 18.1 ± 1.4 | >15 | >25 | ||
| (n = 3) | IA = 2 ± 1% at 1 μM | |||||
| 69 ± 3% at max | ||||||
| M9 | >15 | >25 | >15 | >25 | ||
| M10 | 3.09 ± 0.85 | 1.94 ± 0.06 | >15 | >25 | ||
| IA = 24 ± 2% at 1 μM | ||||||
| 88 ± 12% at max | ||||||
| M11 | 0.099 ± 0.008 | 0.260 ± 0.01 | 2.05 ± 0.43 | 19.8 ± 2.2 | ||
| IA = 78 ± 5% at 1 μM | IA = 4 ± 1% at 1 μM | |||||
| 93 ± 4% at max | 133 ± 5% at max | |||||
| M15 | 3.74 ± 1.32 | 6.89 ± 0.93 | >15 | >25 | ||
| IA = 6 ± 2% at 1 μM | ||||||
| 78 ± 2% at max | ||||||
| M16 | >15 | >25 | >15 | >25 | ||
↵ a IA represents intrinsic activity relative to that of GW2331 for PPARα and rosiglitazone for PPARγ (Devasthale et al., 2005).