AMPK activator 18 is a potent allosteric activator of AMPK complexes containing the β2 isoform. AMPK activator 18activates α2-containing AMPK α2β2γ1 and α2β2γ3 complexes, with EC 50 values of 17.2 and 82.1 nM. AMPK activator 18 stimulates β2-AMPK in cells, and glucose uptake by isolated skeletal muscle. AMPK activator 18 induces acetyl-coenzyme A carboxylase ( ACC ) and AMPK α-T172 phosphorylation. AMPK activator 18 can be used for the research of type 2 diabetes [1].
In Vitro, AMPK activator 18 potently and selectively activates α2-containing AMPK complexes, particularly the skeletal muscle-enriched α2β2γ1 and α2β2γ3 complexes, with EC50 values of 17.2 ± 1.6 nM and 82.1 ± 1.3 nM respectively, and its activation is dependent on the β2-D111 residue but not the β2 N-terminal helix[1]. AMPK activator 18 (0.03-10 μM; 1 h) triggers AMPK signaling in differentiated C2C12 myotubes and β2-reconstituted iMEFs via an allosteric mechanism independent of changes to intracellular AMP/ATP ratio or AMPK α-T172 phosphorylation, inducing dose-dependent ACC phosphorylation[1]. AMPK activator 18 (1-2 μM) increases ACC phosphorylation and AMPK α-T172 phosphorylation levels in Epitrochlearis muscles[1]. AMPK activator 18 (10 μM) reduces 2-deoxyglucose (2DG) uptake in soleus and extensor digitorum longus muscles[1].
References:
[1]. Ngoei K R W, et al. Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog SC4[J]. Cell chemical biology, 2018, 25(6): 728-737. e9.
In Vitro, AMPK activator 18 potently and selectively activates α2-containing AMPK complexes, particularly the skeletal muscle-enriched α2β2γ1 and α2β2γ3 complexes, with EC50 values of 17.2 ± 1.6 nM and 82.1 ± 1.3 nM respectively, and its activation is dependent on the β2-D111 residue but not the β2 N-terminal helix[1]. AMPK activator 18 (0.03-10 μM; 1 h) triggers AMPK signaling in differentiated C2C12 myotubes and β2-reconstituted iMEFs via an allosteric mechanism independent of changes to intracellular AMP/ATP ratio or AMPK α-T172 phosphorylation, inducing dose-dependent ACC phosphorylation[1]. AMPK activator 18 (1-2 μM) increases ACC phosphorylation and AMPK α-T172 phosphorylation levels in Epitrochlearis muscles[1]. AMPK activator 18 (10 μM) reduces 2-deoxyglucose (2DG) uptake in soleus and extensor digitorum longus muscles[1].
References:
[1]. Ngoei K R W, et al. Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog SC4[J]. Cell chemical biology, 2018, 25(6): 728-737. e9.