EX-229

Description: EX229 (AMPK Activator 991) is a benzimidazole analog that is a novel, potent and allosteric AMPK (AMP-activated protein kinase) activator with Kd values of 0.06 uM, 0.06 uM and 0.51 uM for alpha1beta1gamma1, alpha2beta1gamma1 and alpha1beta2gamma1 in biolayer interferometry, respectively. AMPK plays a major role in regulating cellular energy balance by sensing and responding to increases in AMP/ADP concentration relative to ATP. Binding of AMP causes allosteric activation of the enzyme and binding of either AMP or ADP promotes and maintains the phosphorylation of threonine 172 within the activation loop of the kinase. AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases including type 2 diabetes and, more recently, cancer. EX229 activates AMPK in incubated rat epitrochlearis skeletal muscle and incubation of rat skeletal muscle with ex229 increases glucose uptake. The stimulation of skeletal muscle glucose uptake by ex229 is PI3K/PKB-independent, while AMPK-dependent. ex229 increases fatty acid oxidation and glucose uptake in L6 myotubes.

References: Am J Physiol Endocrinol Metab. 2016 Oct 1; 311(4):E706-E719; Nat Commun. 2013; 4:3017. doi: 10.1038/ncomms4017.