| 产品描述： | AMPK 活化剂;AMPK Activators;;InformationMK-3903 MK-3903 is a potent and selective AMPK activator with an EC50 of 8 nM for α1 β1 γ1 subunit. It activates 10 of the 12 pAMPK complexes with EC50 values in the range of 8-40 nM and maximal activation >50%.TargetsAMPK 8 nM(EC50)In vitroMK-3903 activates 10 of the 12 pAMPK complexes with EC50 values in the range of 8-40 nM and maximal activation >50%. The compound partially activates pAMPK5 (36% max), which is only a minor component of human and mouse liver, and it does not activate pAMPK6, which is not detected in liver. MK-3903 is a weak reversible inhibitor of CYP3A4 and 2D6 in human liver microsomes (apparent IC50 > 50 μM) and does not exhibit time-dependent inhibition of CYP3A4 activity. MK-3903 is not a potent PXR agonist.In vivoThe pharmacokinetics of MK-3903 in C57BL/6 mice, Sprague–Dawley rats, and beagle dogs were characterized by moderate systemic plasma clearance (5.0–13 mL/min/kg), a volume of distribution at steady state of 0.6–1.1 L/kg, and a terminal half-life of ∼2 h. It has low oral bioavailability (8.4%) in C57BL/6 mice, but the oral exposure is later improved using other vehicles. Oral bioavailabilities in rats and dogs are improved (27-78%). Chronic oral administration of compound MK-3903 robustly increased ACC phosphorylation in liver with more modest effects in skeletal muscle. Treatment of various mouse models with MK-3903 results in expected alterations in lipid metabolism and improvements in a measure of insulin sensitization. |
| 体内研究： |
MK-3903 (化合物 42) 在 C57BL/6 小鼠、Sprague 至 Dawley 大鼠和比格犬中的药代动力学特征为中度全身血浆清除率 (5.0 至 13 mL/min/kg)，稳态分布容积为 0.6至 1.1 L/kg，终末半衰期约为 2 小时。对喂食高果糖的 db/+ 小鼠急性口服 MK-3903 (3、10 和 30 mg/kg) 可显著抑制所有三种剂量的肝脂肪酸合成 (FAS)。 |
| 参考文献： |
1. Lan P, Romero FA, et al. Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase. J Med Chem. 2017 Nov 9;60(21):9040-9052. |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.198 ml |
10.991 ml |
21.983 ml |
| 5 mM |
0.44 ml |
2.198 ml |
4.397 ml |
| 10 mM |
0.22 ml |
1.099 ml |
2.198 ml |
| 50 mM |
0.044 ml |
0.22 ml |
0.44 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京