Etomoxir (sodium salt)

Etomoxir((R)-(+)-Etomoxir) sodium salt is an irreversible inhibitor of carnitine palmitoyltransferase 1a (CPT-1a), inhibits fatty acid oxidation (FAO) through CPT-1a and inhibits palmitate β-oxidation in human, rat and guinea pig^[1]. IC50 & Target: CPT-1a^[2] In Vitro: Etomoxir mediates differential metabolic channeling of fatty acid and glycerol precursors into cardiolipin in H9c2 cells^[2].
Etomoxir does not affect the activities of the cardiolipin biosynthetic and remodeling enzymes but causes a reduction in [1-¹⁴C]palmitic acid or [1-¹⁴C]oleic acid incorporation into cardiolipin^[2].
Etomoxir increases [1,3-³H]glycerol incorporation into cardiolipin. The mechanism is a 33% increase in glycerol kinase activity, which produces an increased glycerol flux through the de novo pathway of cardiolipin biosynthesis^[2]. In Vivo: Etomoxir significantly inhibits the decrease of bone mineral density (BMD) and bone breaking strength in db/db and high fat (HF)-fed mice and suppresses the reduction of BMSCs-differentiated osteoblasts^[3].
Etomoxir inhibits the increase of mitochondrial ROS generation in db/db and HF-fed mice and osteoblasts^[3].
Etomoxir-induced partial carnitine palmitoyltransferase-I (CPT-I) inhibition in vivo does not alter cardiac long-chain fatty acid uptake and oxidation rates^[4]