Extended Data Fig. 5: EVT0185 inhibits key metabolic enzymes involved in the regulation of sterol and fatty acid synthesis.
From: ACLY inhibition promotes tumour immunity and suppresses liver cancer
a, Graphical representation showing metabolic enzymes in the regulation of sterol and fatty acid synthesis. The graphical representation was created using BioRender (https://biorender.com). (b-c), Effect of BA (Bempedoic acid) and EVT0185 on b, lactate and c, acetate incorporation into fatty acids and sterols in WT and Acly KO mouse hepatocytes. Each stacked bar represents the mean ± SEM, % suppression with BA or EVT0185 in WT (n = 3) and Acly KO (n = 3) mice. (d-g) Inhibitory effect of EVT0185-CoA on the activity of d, AMPK; e, ACC1; f, ACC2; and g, ACSS2. Each line graph represents the mean ± SEM, enzyme activity inhibition by EVT0185-CoA (n = 3 samples/group). (h and i) Effect of Bempedoic acid and EVT0185 on clonogenic survival/colony formation in h, Hep3B human, and i, Hepa1-6 mouse HCC cell lines. Each line graph represents the mean ± SEM colony formation in cells treated with EVT0185 or Bempedoic acid (n = 4 biologically independent samples/treatment groups).
