PF-06409577 is orally bioavailable AMPK activator with EC50 of 7 nM for α1β1γ1 in the TR-FRET assay and it shows no detectable inhibition of hERG in a patch-clamp assay (100 μM) and was not an inhibitor (IC50 > 100 μM) of the microsomal activities of major human cytochrome P450 isoforms.

＞98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

PF 06409577；PF06409577

Powder

DMSO : 34.2 mg/mL (100 mM)

Ethanol : 6.8 mg/mL (20 mM)

AMPK α1β1γ1

In human and rat , PF-06409577 has similar effectiveness for α1β1γ1 isoforms. PF-06409577 exhibits minimal off-target effects on a panel of receptors, ion channels, PDEs, and kinases. PF-06409577 has no inhibition of hERG in a patch-clamp assay (100 ?M) and is not an inhibitor (IC50>100 ?M) of the microsomal activities of major human cytochrome P450 isoforms.

In rats, monkeys, and dogs, PF-06409577 has moderate plasma clearance 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 JPorbed in dogs, rats, and monkeys. The corresponding oral bioavailability values in rats, monkeys, and dogs are 15%, 59%, and 100%, respectively. Dose-dependent 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. Oral administration of PF-06409577 (10, 30, and 100 mg/kg every day) resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2-fold reduction in 24-hour urinary albumin loss compared with vehicle control after 60 days of treatment.