Biological Activity
MK-3903 is a potent and selective AMP-activated protein kinase (AMPK) activator with an EC50 of 8 nM.
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 (Papp=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)[1].
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[1].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.