Etomoxir is a carnitine palmitoyltransferase 1a (CPT-1a) inhibitor that inhibits fatty acid oxidation by inhibiting CPT-1a and inhibits palmitate oxidation in humans, rats, and guinea pigs. Etomoxir has an inhibitory effect on adenine nucleotide translocase and can inhibit macrophage polarization by disrupting CoA homeostasis.

Etomoxir irreversibly binds to the catalytic site of CPT-1, inhibiting its activity but also upregulating fatty acid oxidase. Etomoxir was developed as an inhibitor of mitochondrial carnitine palmitoyltransferase-1 (CPT-1), which is located on the outer membrane of the mitochondria. Etomoxir, acts as a peroxisome proliferator in the liver, increasing DNA synthesis and liver growth. Therefore, in addition to being a CPT1 inhibitor, etomoclax can also be considered a PPARalpha agonist[1]. Etomoxir is a member of the ethylene oxide carboxylate carnitine palmitoyltransferase I inhibitor family and has been suggested as an inhibitor against heart failure. Acute Etomoxir treatment irreversibly inhibits carnitine palmitoyltransferase I activity. As a result, fatty acid import into mitochondria and β-oxidation are reduced, whereas cytosolic fatty acid accumulation and glucose oxidation are increased. Prolonged incubation (24 hours) with Etomoxir produces differential effects on the expression of several metabolic enzymes.[1]

Rats were injected with Etomoxir, daily for 8 days at a dose of 20 mg/kg body weight. Etomoxir-treated rats showed a 44% reduction in cardiac CPT-I activity. Treatment of Lewis rats with 20 mg/kg Etomoxir for 8 days did not alter blood glucose levels, consistent with similar Etomoxir feeding studies. Likewise, Etomoxir feeding did not affect general growth characteristics such as weight gain, nor did it affect hindlimb muscle mass. However, in Etomoxir-treated rats, both heart mass and liver mass were significantly increased by 11%.[3]
Etomoxir is an inhibitor of CPT1, a key enzyme involved in free fatty acid (FFA) oxidation. P53 directly interacts with Bax and Bax is inhibited by Etomoxir, further confirming the direct interaction of P53 and Bax and the involvement of FAO-mediated mitochondrial ROS generation in db/db mice.[2]