Figure 1: ETC-1002-CoA inhibits ACL and mediates β1-selective AMPK activation. | Nature Communications

Figure 1: ETC-1002-CoA inhibits ACL and mediates β1-selective AMPK activation.

From: Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis

Figure 1

Recombinant human ACL was incubated in the presence of the indicated concentrations of ETC-1002-CoA (a–c) or ETC-1002 (d), and (a) coenzyme A (CoA), (b) citrate or (c) ATP. Conversion of [14C]-citrate to [14C]-acetyl-CoA was measured in counts per minute (CPM). Recombinant human (e) AMPKα1β1γ1 and (f) AMPKα1β2γ1 complexes were incubated in the presence of the indicated concentrations of ETC-1002, ETC-1002-CoA, AMP or A-769622. (g) Structure of ETC-1002 and the biochemical reaction that generates ETC-1002-CoA acyl-CoA synthetase (ACS). ETC-1002-CoA/CoASH enzyme ACL kinetic analyses are single measures, and representative results from n=3 independent experiments shown; AMPK activity was determined by time-resolved fluorescence resonance energy transfer expressed as mean±s.e.m. of triplicate measures. (a) Ki calculated by Michaelis–Menten kinetic analysis.

Back to article page