ELOVL1-27 is an inhibitor of ELOVL fatty acid elongase 1 (ELOVL1; IC50 = 900 nM).1 It reduces lysohexacosanoylphosphatidylcholine (LPC(C26:0)) synthesis in HEK293 cells (IC50 = 13 nM), as well as in primary fibroblasts isolated from patients with cerebral adrenoleukodystrophy (CALD) or adrenomyeloneuropathy (AMN; IC50s = 15-43 nM), neurodegenerative diseases characterized by rapid inflammatory demyelination of the CNS. ELOVL1-27 (2, 16, and 32 mg/kg) reduces blood LPC(C26:0) levels in wild-type mice and rats. It also reduces CNS levels of LPC(C26:0) in an ABCD1-/- mouse model of ALD when administered at a dose of 1 or 10 mg/kg per day for at least three months.
1.Come, J.H., Senter, T.J., Clark, M.P., et al.Discovery and optimization of pyrazole amides as inhibitors of ELOVL1J. Med. Chem.64(24)17753-17776(2021)