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Chemical Structure| 1467057-23-3 Chemical Structure| 1467057-23-3

Structure of PF-06409577
CAS No.: 1467057-23-3

Chemical Structure| 1467057-23-3

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PF-06409577 is a potent and selective allosteric activator of AMPK with EC50 value of 7 nM for AMPKα1β1γ1, but >40000 nM for AMPKα1β2γ1.

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Product Details of PF-06409577

CAS No. :1467057-23-3
Formula : C19H16ClNO3
M.W : 341.79
SMILES Code : O=C(C1=CNC2=C1C=C(C3=CC=C(C4(O)CCC4)C=C3)C(Cl)=C2)O
MDL No. :MFCD29917835
InChI Key :FHQXLWCFSUSXBF-UHFFFAOYSA-N
Pubchem ID :71748255

Safety of PF-06409577

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of PF-06409577

epigenetics
PI3K-AKT

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Human primary hepatocytes 255 nM (EC50) 1 hour To evaluate the effect of PF-06409577 on ACC phosphorylation, results showed that PF-06409577 dose-dependently increased phosphorylation of ACC at serine 79 EBioMedicine. 2018 May;31:122-132
Monkey primary hepatocytes 875 nM (EC50) 1 hour To evaluate the effect of PF-06409577 on ACC phosphorylation, results showed that PF-06409577 dose-dependently increased phosphorylation of ACC at serine 79 EBioMedicine. 2018 May;31:122-132
Rat primary hepatocytes 69 nM (EC50) 1 hour To evaluate the effect of PF-06409577 on ACC phosphorylation, results showed that PF-06409577 dose-dependently increased phosphorylation of ACC at serine 79 EBioMedicine. 2018 May;31:122-132
EndoC-βH3 cells 10 or 20 µM 1 hour Significantly stimulated insulin secretion at high glucose concentrations Diabetologia. 2022 Jun;65(6):997-1011
Mouse islets 25 µM 1.5 hours Significantly stimulated insulin secretion at high glucose concentrations Diabetologia. 2022 Jun;65(6):997-1011
Bone marrow-derived macrophages (BMDMs) 10 µM 16 hours PF-06409577 attenuated low glucose-induced MIF release. Diabet Med. 2025 Mar;42(3):e15456
Raw264.7 cells 10 µM 16 hours PF-06409577 attenuated low glucose-induced MIF release. Diabet Med. 2025 Mar;42(3):e15456
BHK-21 cells 50 μg/ml 24 hours To evaluate the inhibitory effect of PF-06409577 on WNV replication, results showed significant reduction in virus yield. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00360-18
Vero cells 50 μg/ml 24 hours To evaluate the effect of PF-06409577 on phosphorylation of AMPK and ACC, results showed significant increase in phosphorylation levels of AMPK and ACC. Antimicrob Agents Chemother. 2018 Jun 26;62(7):e00360-18
MG-63 cells 1 µM 48/72 hours Significantly inhibited cell viability and BrdU incorporation Front Oncol. 2021 Jul 14;11:659181
U2OS cells 0.3-3 µM 48 hours Inhibited cell viability and proliferation, induced cell apoptosis and cell cycle arrest Front Oncol. 2021 Jul 14;11:659181
Primary human OS cells (Pri_OS-1/-2) 1 µM 48/72 hours Significantly inhibited cell viability and BrdU incorporation Front Oncol. 2021 Jul 14;11:659181
SaOs-2 cells 1 µM 48/72 hours Significantly inhibited cell viability and BrdU incorporation Front Oncol. 2021 Jul 14;11:659181
Peritoneal macrophages 10 µM 90 minutes Treatment with PF-06409577 increased AMPK activity, as indicated by increased phosphorylation of ACC. iScience. 2023 Oct 20;26(11):108269
Bone marrow-derived macrophages (BMDMs) 1 µM, 3 µM, 10 µM 90 minutes PF-06409577 dose-dependently activated AMPK as indicated by increased phosphorylation of downstream substrates ULK1 and acetyl-CoA carboxylase (ACC), which are important for autophagy and fatty acid oxidation/de novo lipogenesis, respectively. iScience. 2023 Oct 20;26(11):108269
Embryonic kidney cells 1, 3 or 10 µM From culture day 0 to day 8 To evaluate the inhibitory effect of PF-06409577 on embryonic kidney cyst development. Results showed that PF-06409577 significantly reduced cyst number and size, with >30% inhibition at 10 μM. FEBS Open Bio. 2022 Oct;12(10):1761-1770
MDCK cells 1, 3 or 10 µM From day 5 to day 12 To evaluate the inhibitory effect of PF-06409577 on MDCK cyst growth. Results showed that PF-06409577 significantly inhibited cyst enlargement, with >40% inhibition at 10 μM. FEBS Open Bio. 2022 Oct;12(10):1761-1770

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Pkd1flox/flox;Ksp-Cre ADPKD mouse model Subcutaneous injection 1 or 10 mg/kg/day Once daily from postnatal day 6 to day 12 To evaluate the inhibitory effect of PF-06409577 on renal cyst development in ADPKD mice. Results showed that PF-06409577 significantly reduced kidney size and cyst area, with >35% inhibition at 10 mg/kg. FEBS Open Bio. 2022 Oct;12(10):1761-1770
CB.17 severe combined immunodeficient (SCID) mice U2OS cells and primary human OS cells (Pri_OS-1) xenograft model Oral 10/30 mg/kg Daily for 24 days Significantly inhibited the growth of U2OS and primary OS cell xenografts Front Oncol. 2021 Jul 14;11:659181
Mice High fat diet-induced metabolic syndrome model Oral 100 mg/kg Once daily for 42 days To evaluate the effect of PF-06409577 on hepatic lipids and cholesterol, results showed that PF-06409577 significantly reduced hepatic triacylglycerol (TAG) and cholesterol levels, and decreased mRNA expression of markers of hepatic fibrosis EBioMedicine. 2018 May;31:122-132
Mice ApoE-/- mice and PCSK9 over-expression mouse models Oral gavage 100 mg/kg Once daily for 6 weeks PF-06409577 reduced atherosclerosis in two mouse models in a myeloid-derived AMPK b1 dependent manner, suggesting a critical role for macrophages. iScience. 2023 Oct 20;26(11):108269

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.93mL

0.59mL

0.29mL

14.63mL

2.93mL

1.46mL

29.26mL

5.85mL

2.93mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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