A-769662

SKU: orb1223878

Description

A small molecule AMPK activator that directly stimulates partially purified rat liver AMPK (EC50=0.8 uM) and inhibits fatty acid synthesis in primary rat hepatocytes (IC50=3.2 uM); decreases hepatic expression of PEPCK, G6Pase, and FAS, lowered plasma glucose by 40%, reduces body weight gain and significantly decreases both plasma and liver triglyceride levels in ob/ob mice (30 mg/kg b.i.d.); also directly inhibits Na(+)-K(+)-ATPase, decreases the sodium pump cell surface abundance in L6 skeletal muscle cells.Diabetes Preclinical(In Vitro):A-769662 is equally potent in activating the baculovirus expressed α1,β1,γ1 recombinant isoform of AMPK (EC50=0.7 μM). A-769662 and A-592107 activate AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for A-769662 using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 μM, 1.9 μM, or 1.1 μM, respectively. A-769662 activates endogenous AMPK in LKB1-expressing (HEK293) and LKB1-deficient (CCL13) cells. A-769662 allosterically activates AMPK complexes containing γ1 harboring a substitution of arginine residue 298 to glycine (R298G). A-769662 inhibits dephosphorylation of Thr-172 in the mutant γ1-containing complexes to a similar degree as seen in the wild-type complexes. A769662 (300 μM) has toxic effects on MEF cells. A769662 reversibly inhibits the proteasomal activity.(In Vivo):A-769662 (30 mg/kg, i.p.) significantly reduced the respiratory exchange ratio (RER) in the SD rat. There are 33% and 58% reductions of malonyl CoA levels in livers of animals treated with 30 mg/kg A-769662 (0.905 nmol/g) or 500 mg/kg metformin (0.574 nmol/g), respectively. A-769662 (30 mg/kg, b.i.d.) significantly decreases fed plasma glucose (30%-40% reduction), while the lower doses (3 and 10 mg/kg) of A-769662 had no effect on the in diabetic ob/ob mice.

Key Properties

• CAS Number: 844499-71-4
• MW: 360.3859
• Purity: >98% (HPLC)
• Formula: C₂₀H₁₂N₂O₃S
• SMILES: N#CC1=C(O)C(C(C2=CC=C(C3=CC=CC=C3O)C=C2)=CS4)=C4NC1=O
• Target: AMPK
• Solubility: DMSO: 24 mg/mL

Bioactivity

• In Vivo:
  A-769662 (30 mg/kg, i.p.) significantly reduced the respiratory exchange ratio (RER) in the SD rat. There are 33% and 58% reductions of malonyl CoA levels in livers of animals treated with 30 mg/kg A-769662 (0.905 nmol/g) or 500 mg/kg metformin (0.574 nmol/g), respectively. A-769662 (30 mg/kg, b. i. d.) significantly decreases fed plasma glucose (30%-40% reduction), while the lower doses (3 and 10 mg/kg) of A-769662 had no effect on the in diabetic ob/ob mice.
• In Vitro:
  A-769662 is equally potent in activating the baculovirus expressed α1, β1, γ1 recombinant isoform of AMPK (EC50 = 0.7 μM). A-769662 and A-592107 activate AMPK purified from multiple tissues and species in a dose-responsive manner with modest variations in observed EC50s. EC50s determined for A-769662 using partially purified AMPK extracts from rat heart, rat muscle, or human embryonic kidney cells (HEKs) are 2.2 μM, 1.9 μM, or 1.1 μM, respectively. A-769662 activates endogenous AMPK in LKB1-expressing (HEK293) and LKB1-deficient (CCL13) cells. A-769662 allosterically activates AMPK complexes containing γ1 harboring a substitution of arginine residue 298 to glycine (R298G). A-769662 inhibits dephosphorylation of Thr-172 in the mutant γ1-containing complexes to a similar degree as seen in the wild-type complexes. A769662 (300 μM) has toxic effects on MEF cells. A769662 reversibly inhibits the proteasomal activity.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

A769662 | A 769662

Quick Database Links

Gene Symbol

AMPK