1. Epigenetics
    PI3K/Akt/mTOR
  2. AMPK

A-769662 (Synonyms: A769662; A 769662)

Cat. No.: HY-50662 Purity: 98.80%
Handling Instructions

A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM, and has little effect on GPPase/FBPase activity.

For research use only. We do not sell to patients.
A-769662 Chemical Structure

A-769662 Chemical Structure

CAS No. : 844499-71-4

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10 mM * 1 mL in DMSO $55 In-stock
5 mg $50 In-stock
10 mg $70 In-stock
50 mg $250 In-stock
100 mg $450 In-stock
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Description

A-769662 is a potent, reversible AMPK activator with EC50 of 0.8 μM, and has little effect on GPPase/FBPase activity.

IC50 & Target

EC50: 0.8 μM (AMPK)

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[1]. 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[2]. A769662 (300 μM) has toxic effects on MEF cells. A769662 reversibly inhibits the proteasomal activity[3].

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[1].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.7748 mL 13.8739 mL 27.7477 mL
5 mM 0.5550 mL 2.7748 mL 5.5495 mL
10 mM 0.2775 mL 1.3874 mL 2.7748 mL
Kinase Assay
[1]

To assay glycogen phosphorylase b (GPb) activity, 1.5 μg/mL of rabbit GPb is added to a reaction mix containing 20 mM Na2HPO4 (pH 7.2), 2 mM MgSO4, 1 mM β-NADP (β-nicotinamide adenine dinucleotide phosphate), 1.4 U/mL G-6-PDH (Glucose-6-Phosphate-Dehydrogenase) and 3 U/mL PGM (phosphoglucomutase). AMP or test compounds are added to the assay medium at the specified concentrations followed by the addition of glycogen (final concentration 1 mg/mL) to initiate the reaction. After incubating 10 min at 25°C, GPb activity is assessed by measuring absorbance at 340 nm.

Animal Administration
[1]

A-769662 is formulated in 0.2% hydroxypropyl methylcellulose.

After acclimation ob/ob and lean mice are randomized to the various treatment groups by body weight and fed glucose levels (tail snip) at 8 AM. Baseline plasma insulin samples are also taken from a subset of the animals representing each treatment group (n=10 ob/ob and n=10 lean ob/+ littermates). Two separate ob/ob and lean littermate studies are completed: 1) an initial 5 day study, and 2) a 14 day study to examine efficacy and more completely characterize the body weight change observed in the 5 day study. Treatment groups for the 5 day study are as follows: ob/ob vehicle (0.2% hydroxypropyl methylcellulose [HPMC], i.p., b.i.d.), A-592107 (10 or 100 mg/kg, i.p., b.i.d.), A-769662 (3 or 30 mg/kg, i.p., b.i.d.), AICAR (375 mg/kg, s.c., b.i.d.), or metformin (450 mg/kg, p.o., q.d., with vehicle in PM), and lean littermates treated with vehicle (i.p., b.i.d.). Treatment groups for the 14 day ob/ob and lean littermate study are as follows: ob/ob vehicle (0.2% HPMC, i.p., b.i.d.), A-769662 (3, 10, or 30 mg/kg, i.p., b.i.d.), or metformin, and lean littermates treated with vehicle or 30 mg/kg of A-769662 (i.p., b.i.d.).

References
M.Wt

360.39

Formula

C₂₀H₁₂N₂O₃S

CAS No.

844499-71-4

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 24 mg/mL

Purity: 98.80%

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A-769662
Cat. No.:
HY-50662
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