| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
ELOVL1[1]
ELOVL1-IN-3 targets ELOVL1, a transmembrane enzyme located in the endoplasmic reticulum that catalyzes the elongation of saturated and monounsaturated fatty acids with chain lengths of C18-C22; inhibition of ELOVL1 reduces the production of very long-chain fatty acids. |
|---|---|
| ln Vitro |
In vitro, ELOVL1-IN-3 inhibits ELOVL1 enzymatic activity in cell-free assays and in cultured cells; it reduces the levels of very long-chain fatty acids (C24:0, C26:0, and C26:1) in a dose-dependent manner; it shows selectivity for ELOVL1 over other ELOVL isoforms.
|
| ln Vivo |
In vivo, ELOVL1-IN-3 demonstrates efficacy in reducing VLCFA levels in animal models; it has been evaluated in models of X-linked adrenoleukodystrophy (X-ALD), a disorder characterized by the accumulation of VLCFAs due to ABCD1 deficiency; treatment reduces VLCFA levels in plasma and tissues.
|
| Enzyme Assay |
Non-cellular enzyme assay: ELOVL1-IN-3 is evaluated using microsomal preparations from cells overexpressing ELOVL1; the enzyme activity is measured by incubating microsomes with radiolabeled malonyl-CoA and a fatty acyl-CoA substrate (e.g., C22:0-CoA); the elongation product (C24:0-CoA) is extracted and quantified by scintillation counting or LC-MS; IC₅₀ values are calculated from dose-response curves.
|
| Cell Assay |
Cellular assays: Cells (e.g., fibroblasts from X-ALD patients or ELOVL1-overexpressing cells) are treated with ELOVL1-IN-3 at various concentrations; VLCFA levels are measured by LC-MS or gas chromatography; cell viability is assessed by MTT assay; effects on other lipid species (e.g., phospholipids, sphingolipids) are evaluated by lipidomics.
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| Animal Protocol |
In vivo animal experiments: ELOVL1-IN-3 is administered to mice (e.g., wild-type or X-ALD model mice) via oral gavage or intraperitoneal injection; blood and tissue samples are collected; VLCFA levels in plasma, brain, liver, and adrenal glands are measured by LC-MS; pharmacokinetic parameters, body weight, and organ toxicity are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties: ELOVL1-IN-3 is a small molecule with properties suitable for oral administration; it has moderate bioavailability and brain penetration; it is metabolized by CYP450 enzymes and has a reasonable plasma half-life for once- or twice-daily dosing.
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| Toxicity/Toxicokinetics |
Toxicological profile: ELOVL1-IN-3 is well-tolerated at therapeutic doses in preclinical studies; no significant toxicity has been reported at effective doses; high doses may affect other lipid metabolic pathways; long-term safety studies are ongoing.
|
| References |
[1]. Boyd MJ, et al. Discovery of Novel, Orally Bioavailable Pyrimidine Ether-Based Inhibitors of ELOVL1. J Med Chem. 2021;64(24):17777-17794.
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| Additional Infomation |
Other information: ELOVL1-IN-3 is an investigational compound being developed for the treatment of X-linked adrenoleukodystrophy (X-ALD) and other disorders associated with VLCFA accumulation; it represents a potential therapeutic strategy to normalize VLCFA levels in affected patients.
|
| Molecular Formula |
C21H23N5O2
|
|---|---|
| Molecular Weight |
377.44
|
| Exact Mass |
377.185
|
| CAS # |
2761063-99-2
|
| PubChem CID |
162641713
|
| Appearance |
Colorless to light yellow oil
|
| LogP |
2.6
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
28
|
| Complexity |
497
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N1(C2C=C(O[C@@H]3C[C@H](N4C=CC=N4)C3)N=CN=2)CCO[C@@H](C2=CC=CC=C2)C1
|
| InChi Key |
JXGFJBHPOCYADP-CTWPCTMYSA-N
|
| InChi Code |
InChI=1S/C21H23N5O2/c1-2-5-16(6-3-1)19-14-25(9-10-27-19)20-13-21(23-15-22-20)28-18-11-17(12-18)26-8-4-7-24-26/h1-8,13,15,17-19H,9-12,14H2/t17?,18?,19-/m1/s1
|
| Chemical Name |
(2S)-2-phenyl-4-[6-(3-pyrazol-1-ylcyclobutyl)oxypyrimidin-4-yl]morpholine
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~264.94 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6494 mL | 13.2471 mL | 26.4943 mL | |
| 5 mM | 0.5299 mL | 2.6494 mL | 5.2989 mL | |
| 10 mM | 0.2649 mL | 1.3247 mL | 2.6494 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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