1. Epigenetics
    PI3K/Akt/mTOR
  2. AMPK

PF-06409577 

Cat. No.: HY-103683 Purity: 98.56%
Handling Instructions

PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM.

For research use only. We do not sell to patients.

PF-06409577 Chemical Structure

PF-06409577 Chemical Structure

CAS No. : 1467057-23-3

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 77 In-stock
Estimated Time of Arrival: December 31
5 mg USD 70 In-stock
Estimated Time of Arrival: December 31
10 mg USD 120 In-stock
Estimated Time of Arrival: December 31
25 mg USD 280 In-stock
Estimated Time of Arrival: December 31
50 mg USD 480 In-stock
Estimated Time of Arrival: December 31
100 mg USD 810 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

PF-06409577 is a potent and selective allosteric activator of AMPK α1β1γ1 isoform with an EC50 of 7 nM.

IC50 & Target[1]

AMPK α1β1γ1

7 nM (EC50)

In Vitro

PF-06409577 possesses similar potency toward the human and rat α1β1γ1 isoforms. In broad panel screening against other receptors, channels, PDEs and kinases, PF-06409577 exhibits minimal off-target pharmacology. PF-06409577 shows no detectable inhibition of hERG in a patch-clamp assay (100 µM) and is not an inhibitor (IC50>100 µM) of the microsomal activities of major human cytochrome P450 isoforms[1].

In Vivo

PF-06409577 demonstrates moderate plasma clearance in rats, dogs, and monkeys, and is well distributed with steady state distribution volume. Following oral administration of crystalline PF-06409577 in 0.5% methylcellulose suspension, PF-06409577 is rapidly absorbed in rats, dogs, and monkeys. The corresponding oral bioavailability values in rats, dogs, and monkeys, are 15%, 100%, and 59%, respectively. Dose responsive increases in pAMPK relative to total AMPK (tAMPK) in whole kidney tissue are observed with a maximal 3.8-fold response at 300 mg/kg PF-06409577 treatment[1]. Oral administration of PF-06409577 (10, 30, and 100 mg/kg QD) results in dose-dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2-fold reduction in 24-hour urinary albumin loss compared to vehicle control after 60 days of treatment[1].

Clinical Trial
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (292.58 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.9258 mL 14.6289 mL 29.2577 mL
5 mM 0.5852 mL 2.9258 mL 5.8515 mL
10 mM 0.2926 mL 1.4629 mL 2.9258 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[1]

PF-06409577 is prepared in DMSO. PF-06409577 is incubated with fully phosphorylated AMPK in assay buffer at room temperature for 15 min followed by addition of PP2a and another incubation for 60 min at room temperature. The phosphatase treatment is quenched and the kinase assay initiated with the addition of okadaic acid (50 nM final), 50 nM Cy-5 SAMS peptide and ATP equal to Km for each isoform. Reactions are incubated for an additional 60 min and the kinase reaction is quenched with the addition of 10 mM EDTA and 2 nM Eu-pACC antibody in detection Buffer. Kinase activity is monitored by excitation at 320 nM and measuring emission at 665 and 615 nM, respectively[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Rats: Daily administration of 0.5% methylcellulose (p.o.), PF-06409577 at 10, 30, or 100 mg/kg (p.o.), PF- 249 at 3, 10, or 30 mg/kg (p.o.), or ramipril in drinking water (1 mg/kg/day) is initiated and continued for 68 days. Urine is collected for 24-hours and volume recorded from all lean and obese rats after 14, 28, 42, and 60 days of dosing. On Day 63 all rats are administered a final dose after 16-hour overnight fasting. One hour following the final dose, blood glucose is measured by glucometer and a 100 μL tail vein blood sample collected and processed for determination of insulin levels and total protein. Each rat is then anesthetized with isoflurane. The right kidney is collected and immediately freeze-clamped and transferred to liquid nitrogen storage; the left kidney is fixed in 10% formalin. Rats are then euthanized by exsanguination from the vena cava[1]

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

341.79

Formula

C₁₉H₁₆ClNO₃

CAS No.

1467057-23-3

SMILES

O=C(C1=CNC2=C1C=C(C3=CC=C(C4(O)CCC4)C=C3)C(Cl)=C2)O

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

Purity: 98.56%

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Product Name:
PF-06409577
Cat. No.:
HY-103683
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PF-06409577

Cat. No.: HY-103683