251303-04-5
基本信息
Ertiprotafib
Benzenepropanoic acid, a-[4-(9-bromo-2,3-dimethylnaphtho[2,3-b]thien-4-yl)-2,6-dimethylphenoxy]-,(aR)-
Benzenepropanoic acid, α-[4-(9-bromo-2,3-dimethylnaphtho[2,3-b]thien-4-yl)-2,6-dimethylphenoxy]-, (αR)-
物理化学性质
| 沸点 | 690.7±55.0 °C(Predicted) |
| 密度 | 1.376±0.06 g/cm3(Predicted) |
| 储存条件 | -20°C储存 |
| 溶解度 | 溶于二甲基亚砜 |
| 酸度系数(pKa) | 3.21±0.10(Predicted) |
常见问题列表
|
PTP1B 1.6 μM (IC 50 ) |
IKK-β 400 nM (IC 50 ) |
PPARα ~1 μM (EC 50 ) |
PPARβ ~1 μM (EC 50 ) |
Ertiprotafib is a potent inhibitor of IKK-β, with an IC 50 value of 400±40 nM, which is much lower than that required for the half-maximal inhibition of the p-nitrophenyl phosphatase activity of PTP1B. The reported IC 50 value of Ertiprotafib against PTP1B ranges from 1.6 to 29 μM depending on the assay conditions. Ertiprotafib is at least a dual PPARα and PPARβ agonist with EC 50 values for transactivation of 1 μM. Such activities readily explain the observations with suprapharmacologic doses of these.
As seen with treatment of ob/ob mice, both Ertiprotafib and compound 3 seem to significantly improve glucose metabolism in rats. At 25 mg/kg/day, these compounds decrease both fasting blood glucose and insulin levels compared with vehicle treated rats. Furthermore, both Ertiprotafib and compound 3 increase glucose disposal after an oral challenge. It is noteworthy that lipid levels are also reduced in treated animals. Both triglyceride and free fatty acid levels are substantially reduced in rats treated with 25 mg/kg/day of either compound. To summarize, both Ertiprotafib and compound 3 seem to be robust agents in improving glucose utilization in fa/fa rats while also decreasing lipid levels in these animals. Decreased lipid levels may be unexpected for a pure PTP1b inhibitor. It is more telling, as mentioned above, that rats treated with suprapharmacologic doses of Ertiprotafib show signs of PPAR family activation.