PF-06409577

PF-06409577 is a potent and selective small molecule allosteric activator of adenosine monophosphate-activated protein kinase (AMPK), specifically targeting the α1β1γ1 isoform with an EC50 of 7 nM. It exhibits minimal off-target effects on other receptors, ion channels, phosphodiesterases, and kinases. The compound acts by binding to the allosteric drug and metabolite (ADaM) site of AMPK, preventing its dephosphorylation and activating β1-containing isoforms while showing much lower potency for β2-containing isoforms. Developed by Pfizer for potential treatment of diabetic nephropathy, it demonstrated efficacy in preclinical models by improving kidney function and reducing proteinuria. Additionally, it has shown antiviral activity against flaviviruses such as West Nile virus (WNV), Zika virus (ZIKV), and dengue virus (DENV), likely through modulation of host cell lipid metabolism[2][4][5][6].

Other names

6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid