Description
PF-06409577 is an activator of AMP-activated protein kinase (AMPK) heterotrimers (K
d = 9 nM for α1β1γ1).
In vitro, it selectively activates β1-containing AMPK isoforms (EC
50s = 2.18-7.03 nM) over β2-containing isoforms (EC
50s = ≥10 μM). PF-06409577 has an EC
50 value of 7 nM in an activation/protection TR-FRET assay using α1β1γ1 AMPK.
In vivo, PF-06409577 (≥10 mg/kg) increases phosphorylation of AMPK in rat kidney. It decreases urinary albumin levels in a ZSF1 obese rat model of diabetes, metabolic syndrome, and renal disease when administered at a dose of 100 mg/kg.
Biochem/physiol Actions
PF-06409577 preserves retinal pigment epithelium cells from UV radiation by activating AMPK (AMP-activated protein kinase) signaling. This orally bioavailable and possesses pharmacokinetic properties. PF-06409577 blocks de novo lipid and cholesterol synthesis pathways that shows a decrease in hepatic lipids and mRNA expression of markers of hepatic fibrosis.
