LY518674 is a potent and selective PPAR-alpha antagonist with EC50 of 42 nM for human PPARα. LY518674 upregulates both ApoA-I production and catabolism in human subjects with the metabolic syndrome. LY518674 produced a dose-dependent increase in serum HDL-c, resulting in 208 +/- 15% elevation at optimum dose. In cultured hepatocytes, LY518674 produced 50% higher apoA-1 secretion, which was associated with increase in radiolabeled methionine incorporation in apoA-1.
| Molecular Weight | 409.48 |
| Formula | C23H27N3O4 |
| CAS Number | 425671-29-0 |
| Solubility (25°C) | DMSO ≥ 100 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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