Figure 6: The mechanism of action of ETC-1002. | Nature Communications

Figure 6: The mechanism of action of ETC-1002.

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

Figure 6

In liver, ETC-1002 (bempedoic acid) is activated to ETC-1002-CoA by ACSVL1, and subsequently inhibits ACL. Similar to inhibition of HMG-CoA reductase (HMGR) by statins, inhibition of liver ACL by ETC-1002-CoA results in the suppression of cholesterol synthesis and compensatory LDLR upregulation and LDL particle clearance from the blood. Skeletal muscle does not express ACSVL1 and is unable to convert ETC-1002 to its active form. Therefore, ETC-1002 does not suppress the synthesis of cholesterol or the associated biological intermediates that are required to maintain normal muscle cell function, or promote the associated toxicity. Green and red arrows indicate the effects of ETC-1002 and statins, respectively.

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