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MK-3903

CAS No. : 1219737-12-8

MCE 国际站：MK-3903

产品活性：MK-3903 是一种有效且有选择性的 AMP 激活的蛋白激酶 (AMPK) 激活剂，其 EC₅₀ 值为 8 nM。

研究领域：Epigenetics  |  PI3K/Akt/mTOR

作用靶点：AMPK

In Vitro: MK-3903 (compound 42) is a potent and selective AMP-activated protein kinase (AMPK) activator with an EC₅₀ of 8 nM. MK-3903 activates 10 of the 12 phosphorylated AMPK (pAMPK) complexes with EC₅₀ values in the range of 8 to 40 nM and maximal activation >50%. MK-3903 partially activates pAMPK5 (36% max) and it does not activate pAMPK6. MK-3903 demonstrates low permeability (P_app=6×10^-6 cm/s) in LLC-PK1 cells42 and is a substrate of human liver uptake transporters OATP1B1 and OATP1B3 (organic anion transporter proteins). Results show that MK-3903 binds moderately to the prostanoid DP2 (CRTH2) receptor (binding IC₅₀=1.8 μM) but not in the presence of 10% human serum (binding IC₅₀>86 μM).

In Vivo: The pharmacokinetics of MK-3903 (compound 42) in C57BL/6 mice, Sprague to Dawley rats, and beagle dogs are characterized by moderate systemic plasma clearance (5.0 to13 mL/min/kg), a volume of distribution at steady state of 0.6 to 1.1 L/kg, and a terminal halflife of ~2h. Acute oral administration of MK-3903 (3, 10, and 30 mg/kg) to high-fructose fed db/+ mice results in significant inhibition of hepatic fatty acid synthesis (FAS) for all three doses.

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