AMG-221 是 11β-羟基类固醇脱氢酶 1 (11β-HSD1) 抑制剂，Ki为 12.8 nM，IC50为 10.1 nM。AMG-221 可用于 2 型糖尿病的研究。
| 生物活性 | AMG-221 is an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) with aKiof 12.8 nM in vitro biochemical scintillation proximity assay (SPA) and anIC50of 10.1 nM in cell-based assays[1][2]. AMG-221 can be used for the research of type 2 diabetes[3]. |
体外研究
(In Vitro) | AMG-221 shows selectivity over 11β-HSD2, 17β-HSD1, and glucocorticoid receptor (GR) (IC50 values for all assays are >10 μM)[2].
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体内研究
(In Vivo) | AMG-221 (25 or 50 mg/kg; b.i.d.; orally gavaged) inhibits 11β-HSD1 activity in DIO mice. At the end of the study, fed blood glucose shows statistically significant reduction in comparison to the vehicle group. On day 14 and after a 12 h fast, glucose tolerance is slightly improved in the AMG-221 treatment groups compared with the vehicle group[2].
11β-HSD1 activity is inhibited by 33%, 55%, and 47% in the inguinal fat at 4 h after AMG-221 is orally gavaged at 5, 15, and 50 mg/kg, respectively. At 8 h, the 11β-HSD1 activity in the inguinal fat of the 5 mg/kg group has returned to a level (~10% inhibition) close to that in the control animals treated with vehicle, but there is still significant inhibition in the 15 and 50 mg/kg groups (36% and 39% inhibition, respectively)[2].
AMG-221 has a good bioavailability in mouse, rat, and dog. However, the bioavailability in monkey is low[2].
AMG-221 exhibits moderate oral bioavailability (male CD1 mouse 31%) following oral administration (10 mg/kg)[3].
AMG-221 exhibits terminal elimination half-life (male CD1 mouse 3.32 h) due to high plasma clearance (3.31 L/h/kg) combined with large volumes of distribution (0.9 L/kg) following intravenous administration (2 mg/kg)[3].
| Animal Model: | Diet-Induced Obesity (DIO) Mice[2] | | Dosage: | 25 or 50 mg/kg (prepare in 0.1% Tween-80 and 0.5% CMC in water) | | Administration: | Orally gavaged; twice a day for 13 or 14 days | | Result: | There were statistically significant decreases in insulin levels in all treated groups when compared with the vehicle control group on day 13. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
