MK-3903

SKU: orb1302014

Description

MK-3903 is a highly potent and selective activator of AMP-activated protein kinase (AMPK), exhibiting an EC50 of 8 nM. This small molecule is a valuable research tool for investigating AMPK's role in metabolic disorders, such as diabetes and obesity, in both cellular and animal studies.

Research Area

Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 1219737-12-8
• MW: 454.9
• Purity: 98.63% (May vary between batches)
• Formula: C₂₇H₁₉ClN₂O₃
• SMILES: Cc1ccc(Oc2nc3cc(Cl)c(cc3[nH]2)-c2ccc(cc2)-c2ccccc2)cc1C(O)=O
• Target: AMPK
• Solubility: Ethanol:Insoluble;10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.4 mM);DMSO:50 mg/mL (109.91 mM);H2O:Insoluble

Bioactivity

• Target IC50:
  AMPK:8 nM (EC50, cell free)
• In Vivo:
  The pharmacokinetics of MK-3903 in C57BL/6 mice, SD 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 half-life of ~2h. In high-fructose fed db/+ mice, Acute oral administration of MK-3903 (3, 10, and 30 mg/kg) results in significant inhibition of hepatic fatty acid synthesis (FAS) for all three doses.
• In Vitro:
  MK-3903 activates 10 of the 12 phosphorylated AMPK (pAMPK) complexes with EC50 values in the range of 8 to 40 nM. MK-3903 partially activates pAMPK5 (36% max) and it does not activate pAMPK6. MK-3903 demonstrates low permeability in LLC-PK1 cells and is a substrate of human liver uptake transporters OATP1B1 and OATP1B3 (organic anion transporter proteins). MK-3903 binds moderately to the prostanoid DP2 (CRTH2) receptor (IC50: 1.8 μM) but not in the presence of 10% human serum (binding IC50>86 μM).
• Animal Research:
  DIO mice at 17 weeks of age are used in this study. Mice are conditioned to dosing with vehicle (5% Tween 80, 0.25% methylcellulose, 0.02% SDS) at 5 mL/kg BID for 5 days. At that time, mice are bled, glucose and insulin measured and the animals sorted into treatment groups based on glucose, insulin and body weight. Each group of animals receives the administration of MK-3903 in a vehicle at 3 mg/kg, 10 mg/kg, 30 mg/kg, or vehicle alone for 12-day BID. Another group of mice receiving MK-3903 with the vehicle at 30 mg/kg for 12-day QD is included as well. Food intake and body weight are measured daily.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

AMPK, AMP-activated protein kinase, Inhibitor, inhibit, MK 3903, MK3903, MK-3903

Compound Identifiers

PubChem CID

45256689