ELOVL1-22 is a selective inhibitor of ELOVL fatty acid elongase 1 (ELOVL1) that penetrates the blood-brain barrier. ELOVL1-22 can be used for research related to X-linked adrenoleukodystrophy and solid tumor immunotherapy[1-4].
In vitro, HEK293 cells were treated with ELOVL1-22 (100nM) for 48 hours. ELOVL1-22 reduced the synthesis of C24:0 and C26:0 lysophosphatidylcholine (LPC) while causing an accumulation of C20:0 LPC[1]. HeLa cells were co-treated with ELOVL1-22 (0.25µM) and d3-1-deoxySa for 24 hours. ELOVL1-22 significantly reduced the metabolic flux of d3-1-deoxySa into very-long-chain (VLC) 1-deoxydihydroceramide species and led to a compensatory increase in long-chain (LC) 1-deoxydihydroceramide species, significantly reducing 1-deoxySa-induced cytotoxicity[2].
In vivo, ABCD1 knockout (KO) mice (an ALD mouse model) were orally administered ELOVL1-22 (1–32mg/kg) once daily for 3 months. ELOVL1-22 (1–32 mg/kg) was administered orally once daily for 3 months to treat ABCD1 knockout (KO) mice (ALD mouse model). ELOVL1-22 significantly reduced the levels of C26:0 lysophosphatidylcholine (LPC) in plasma and brain in a concentration-dependent manner[1].
References:
[1] Boyd MJ, Collier PN, Clark MP, et al. Discovery of Novel, Orally Bioavailable Pyrimidine Ether-Based Inhibitors of ELOVL1. J Med Chem. 2021 Dec 23;64(24):17777-17794.
[2] Adam Majcher, Gergely Karsai, Elkhan Yusifov, et al. Very long-chain fatty acids drive 1-deoxySphingolipid toxicity. Nat Commun. 2025 Nov 26;16(1):11650.
[3] Schackmann MJ, Ofman R, Dijkstra IM, et al. Enzymatic characterization of ELOVL1, a key enzyme in very long-chain fatty acid synthesis. Biochim Biophys Acta. 2015 Feb;1851(2):231-7.
[4] Ohno Y, Suto S, Yamanaka M, et al. ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18439-44.
ELOVL1-22是一种具有选择性且能穿透血脑屏障的ELOVL脂肪酸延长酶1（ELOVL1）抑制剂。ELOVL1-22可用于X-连锁肾上腺脑白质营养不良和实体瘤免疫治疗的相关研究[1-4]。
在体外，将ELOVL1-22（100nM）处理HEK293细胞48小时。ELOVL1-22降低了C24:0和C26:0溶血磷脂酰胆碱（LPC）的合成，同时导致C20:0 LPC累积[1]。ELOVL1-22（0.25µM）与d3-1-deoxySa共同处理HeLa细胞24小时。ELOVL1-22显著减少了d3-1-deoxySa代谢流向极长链（VLC）1-脱氧二氢神经酰胺物的形成，并导致长链（LC）1-脱氧二氢神经酰胺物的代偿性增加，显著降低了1-deoxySa诱导的细胞毒性[2]。
在体内，将ELOVL1-22（1–32mg/kg）每日一次口服给药，用于处理ABCD1敲除（KO）小鼠（ALD小鼠模型）3个月。ELOVL1-22以浓度梯度的方式显著降低了血浆和大脑中的C26:0溶血磷脂酰胆碱（LPC）水平[1]。