Eliglustat |
Catalog No.GC19392
One-Click Copy Product Info
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엘리글루스타트(Eliglustat)는 24nM의 IC50을 갖는 특이적이고 강력하며 경구 활성인 글루코세레브로시드 합성효소 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 491833-29-5
Sample solution is provided at 25 µL, 10mM.
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Eliglustat is a specific, potent, orally active glucosylceramide synthase (GCS) inhibitor with IC50 of 24nM[1]. Eliglustat inhibits uridine diphosphate (UDP)-glucose ceramide glucosyltransferase-mediated glucose transfer from UDP-glucose to ceramide, thereby reducing glucosylceramide and downstream glycosphingolipid (GSL) synthesis and altering ceramide-dependent autophagy[1,4,5]. Eliglustat is used in research on Gaucher disease substrate accumulation, sphingolipid metabolism, insulin resistance, osteoclastogenesis, tumor-cell metabolism, myeloma bone disease, and Fabry disease substrate reduction[1-5].
In vitro, Eliglustat (0.6nM-1000nM; 72h) concentration-dependently reduced cell-surface ganglioside GM1 in K562 cells and ganglioside GM3 in B16/F10 melanoma cells, with mean IC50 values of 24nM and 29nM, respectively[1]. Eliglustat (128μM; 6h) increased intracellular ceramides and reduced GSLs in RM-9 and PC-3M prostate cancer cells, increased microtubule-associated protein 1 light chain 3 beta-II (LC3B-II), phosphatase and tensin homolog-induced kinase 1 (PINK1), and Parkin, and promoted mitochondrial fragmentation and lysosomal colocalization[4]. Eliglustat (0.1μM, 1μM, 10μM, 25μM, and 50μM; continuous exposure during 5-day culture with 50ng/mL macrophage colony-stimulating factor and 75ng/mL receptor activator of nuclear factor-κB ligand) concentration-dependently reduced tartrate-resistant acid phosphatase-positive osteoclast formation and multinucleation in RAW264.7 cells[5].
In vivo, Eliglustat (75mg/kg/day and 150mg/kg/day; oral gavage once daily for 10 weeks) dose-dependently reduced glucosylceramide accumulation and Gaucher-cell number in the liver, lung, and spleen of young D409V/null Gaucher mice[1]. Eliglustat (150mg/kg/day; oral intake in medicated chow ad libitum for 10 weeks) reduced lysosomal glucosylceramide in symptomatic D409V/null mice and limited renewed substrate accumulation following enzyme-mediated clearance[2]. Eliglustat (300mg/kg/day; oral intake in medicated chow ad libitum for 3-10 months) reduced plasma glucosylceramide and glucosylsphingosine and suppressed monoclonal paraprotein formation, lymphoma, and plasmacytoma development in inducible Gaucher mice[3]. Eliglustat (150mg/kg/day; oral intake in medicated chow ad libitum for 19 days) increased trabecular bone volume and trabecular number and reduced osteoclast indices in female C57BL/6J mice[5].
References:[1] McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007;91(3):259-267. doi:10.1016/j.ymgme.2007.04.001.
[2] Marshall J, McEachern KA, Chuang WL, Hutto E, Siegel CS, Shayman JA, et al. Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy. J Inherit Metab Dis. 2010;33(3):281-289. doi:10.1007/s10545-010-9072-z.
[3] Pavlova EV, Archer J, Wang SZ, Dekker N, Aerts JM, Karlsson S, Cox TM. Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy. J Pathol. 2015;235(1):113-124. doi:10.1002/path.4452.
[4] Vykoukal J, Fahrmann JF, Gregg JR, Tang Z, Basourakos S, Irajizad E, et al. Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer. Nat Commun. 2020;11(1):4279. doi:10.1038/s41467-020-17645-z.
[5] Leng H, Zhang H, Li L, Zhang S, Wang Y, Chavda SJ, et al. Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease. Nat Commun. 2022;13(1):7868. doi:10.1038/s41467-022-35358-3.
| Cell experiment [1]: | |
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Cell lines |
RAW264.7 cell model of osteoclast differentiation |
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Preparation Method |
RAW264.7 cells were differentiated in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand and exposed to different Eliglustat concentrations. Tartrate-resistant acid phosphatase-positive osteoclast number, multinucleation, and cell viability were evaluated on culture day 5. |
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Reaction Conditions |
0.1μM, 1μM, 10μM, 25μM, and 50μM; 5 days |
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Applications |
Eliglustat concentration-dependently reduced tartrate-resistant acid phosphatase-positive osteoclast number, nuclei per cell, and osteoclast-covered area and inhibited RAW264.7 cell differentiation into mature osteoclasts. |
| Animal experiment [2]: | |
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Animal models |
High-fat-diet-induced obese C57BL/6 mouse model of insulin resistance |
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Preparation Method |
C57BL/6 mice received a high-fat diet for 8 weeks to establish obesity and insulin resistance and then received oral Eliglustat. Hemoglobin A1c, glucose tolerance, hepatic triglycerides, and hepatic glucose production during a hyperinsulinemic-euglycemic clamp were evaluated. |
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Dosage form |
125mg/kg/day |
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Applications |
Eliglustat lowered hemoglobin A1c and hepatic triglycerides, improved glucose tolerance, and increased insulin-mediated suppression of hepatic glucose production, thereby enhancing hepatic insulin sensitivity. |
| References [1] Leng H, Zhang H, Li L, Zhang S, Wang Y, Chavda SJ, et al. Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease. Nat Commun. 2022;13(1):7868. doi:10.1038/s41467-022-35358-3. [2] Yew NS, Zhao H, Hong EG, Wu IH, Przybylska M, Siegel C, et al. Increased hepatic insulin action in diet-induced obese mice following inhibition of glucosylceramide synthase. PLoS One. 2010;5(6):e11239. doi:10.1371/journal.pone.0011239. | |
| Cas No. | 491833-29-5 | SDF | |
| Canonical SMILES | CCCCCCCC(N[C@H](CN1CCCC1)[C@@H](C2=CC=C(OCCO3)C3=C2)O)=O | ||
| Formula | C23H36N2O4 | M.Wt | 404.54 |
| Solubility | Water : ≥ 50 mg/mL (52.13 mM);DMSO : ≥ 50 mg/mL (52.13 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4719 mL | 12.3597 mL | 24.7194 mL |
| 5 mM | 494.4 μL | 2.4719 mL | 4.9439 mL |
| 10 mM | 247.2 μL | 1.236 mL | 2.4719 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)