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。
Cas No.:2761063-99-2
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | HeLa cells (human epithelial immortal cell line) |
Preparation Method | HeLa cells were supplemented with d3-1-deoxySa (1-deoxysphinganine) in the presence or absence of the ELOVL1-22 (0.25µM). |
Reaction Conditions | 0.25µM; 24h. |
Applications | Co-treatment with ELOVL1-22 significantly reduced the metabolic flux of d3-1-deoxySa into very-long-chain (VLC) 1-deoxyDHCer species (m18:0/24:0 and m18:0/24:1) and caused a compensatory increase in long-chain (LC) 1-deoxyDHCer species (m18:0/16:0, m18:0/18:0, m18:0/20:0), resulting in significant protection from 1-deoxySa-induced cytotoxicity. In separate functional assays, ELOVL1-22 fully restored the loss of mitochondrial respiration (OCR) and glycolytic capacity (ECAR) induced by 1-deoxySa. |
| Animal experiment [2]: | |
Animal models | ABCD1 knockout (KO) mice (a murine model of X-linked adrenoleukodystrophy) and wild-type (WT) mice |
Preparation Method | ABCD1 KO mice received ELOVL1-22 (1–32mg/kg) orally once daily for 3 months. Serial blood samples were collected throughout the study, and brain samples were assessed at 1 and 3 months. |
Dosage form | 1–32mg/kg; orally; once daily for 3 months. |
Applications | ELOVL1-22 induced a dose-responsive decrease in blood C26:0/C16:0 lysophosphatidylcholine (LPC) levels within 1 week of dosing. Doses of 8mg/kg and greater reduced blood C26:0/C16:0 LPC to near wild-type levels. After 3 months of dosing, ELOVL1-22 yielded 27-39% reductions in brain C26:0/C16:0 LPC levels. |
References: | |
| Cas No. | 2761063-99-2 | SDF | Download SDF |
| Canonical SMILES | N1(C2=NC=NC(O[C@H]3C[C@@H](N4C=CC=N4)C3)=C2)C[C@H](C5=CC=CC=C5)OCC1 | ||
| 分子式 | C21H23N5O2 | 分子量 | 377.4 |
| 溶解度 | Ethanol: 25 mg/ml | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6497 mL | 13.2485 mL | 26.4971 mL |
| 5 mM | 529.9 μL | 2.6497 mL | 5.2994 mL |
| 10 mM | 265 μL | 1.3249 mL | 2.6497 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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