MK-3903

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MK-3903 是一种有效的、选择性的、直接的口服 AMPK 激活剂，EC50 为 9 nM。

MK-3903 is a potent and selective, direct and oral AMPK activator with EC50 of 9 nM; activates 10 of the 12 phosphorylated AMPK (pAMPK) complexes with EC50s of 8-40 nM, improves lipid metabolism and insulin sensitization in mice.

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).

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.

MK3903

Membrane Transporter/Ion Channel

AMPK

AMPK

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1219737-12-8

454.91

C27H19ClN2O3

>98% (HPLC)

DMSO: 70 mg/mL; Water: Insoluble; Ethanol: Insoluble （ < 1 mg/ml refers to the product slightly soluble or insoluble )

CC1=C(C=C(C=C1)OC2=NC3=C(N2)C=C(C(=C3)C4=CC=C(C=C4)C5=CC=CC=C5)Cl)C(=O)O

5-[(5-[1,1'-Biphenyl]-4-yl-6-chloro-1H-benzimidazol-2-yl)oxy]-2-methylbenzoic acid

(-20℃)

With Ice Pack

≥ 2 years