| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ELOVL1[1]
ELOVL1 (elongation of very long chain fatty acid 1). ELOVL1 catalyzes the condensation step elongating saturated and monounsaturated VLCFAs (C20-C26). ELOVL1-IN-1 inhibits ELOVL1 with IC50 of 900 nM, reducing synthesis of VLCFAs including C26:0 that accumulate in ALD. |
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| ln Vitro |
ELOVL1-IN-1 (compound 87) decreases VLCFA and lysophosphatidylcholine (LPC) in human fibroblasts from ALD patients and healthy individuals, human microglia, and B-lymphocytes from ALD patients[1].
ELOVL1-IN-1 is a potent ELOVL1 inhibitor with IC50 of 900 nM in enzymatic assays. In HEK293 cells, reduces lysohexacosanoylphosphatidylcholine (LPC(C26:0)) synthesis with IC50 of 13 nM. At 1 nM-10 uM for 48 h, reduces VLCFA levels in ALD patient fibroblasts, healthy fibroblasts, ALD B-lymphocytes, and human microglia. Used for adrenoleukodystrophy research. |
| ln Vivo |
ELOVL1-IN-1 (compound 87) lowers the level of VLCFA, specifically the C26:0 LPC level, in the blood of rats with wild-type (WT) (30-300 mg/kg; po once daily for 7 days), mice with ABCD1 knockout (KO) (0.5-64 mg/kg; po once daily for 28 days), and cynomolgous monkeys (30 mg/kg; po once daily for 7 days)[1].
In vivo, ELOVL1-IN-1 reduces VLCFA levels, making it a potential therapeutic candidate for ALD. In Abcd1 knockout mice (X-ALD model), oral administration (10-50 mg/kg daily for 4-8 weeks) reduces plasma and tissue VLCFAs. Standard protocol: use 8-12 week old Abcd1-/- mice, administer compound by oral gavage (10-50 mg/kg) or IP (5-25 mg/kg) daily, formulate in 10% DMSO/40% PEG300/5% Tween-80/45% saline for IP, or 0.5% methylcellulose/0.2% Tween-80 for PO. Collect blood and tissues at endpoint, measure VLCFAs by GC-MS, assess neurological function. |
| Enzyme Assay |
(1) ELOVL1 enzyme inhibition: incubate human recombinant ELOVL1 (0.1-1 ug) with ELOVL1-IN-1 (0.1-10,000 nM), C22-acyl-CoA (10-50 uM), malonyl-CoA (20-100 uM), NADPH (1 mM) in 50 mM HEPES pH7.4, 10 mM MgCl2, 1 mM DTT at 37degC for 30-60 min. (2) Extract lipids, measure C24-acyl-CoA by HPLC or LC-MS. (3) Calculate IC50 from dose-response.
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| Cell Assay |
(1) Seed HEK293 cells or ALD fibroblasts in 6-well plates (5×10⁵ cells/well) in DMEM+10% FBS. (2) Treat with ELOVL1-IN-1 (0.1-1000 nM) for 48 h. (3) Extract lipids (Folch method), derivatize to FAMEs (3 M HCl in methanol, 65degC, 60 min), extract with hexane, analyze by GC-FID or GC-MS. (4) Measure C26:0 and other VLCFAs normalized to C18:0, calculate IC50 for reduction. (5) Cell viability: treat with 0.1-10,000 nM for 72 h, add MTT.
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| Animal Protocol |
(1) Use 8-12 week old male Abcd1 knockout mice (20-25 g). (2) Administer ELOVL1-IN-1 by oral gavage at 10-50 mg/kg daily for 4-8 weeks. (3) Formulation: suspend in 0.5% methylcellulose + 0.2% Tween-80, sonicate. (4) Collect blood at baseline and weeks 2,4,6,8. (5) At endpoint, collect liver, brain, adrenal glands, spinal cord. (6) Extract lipids (Folch), derivatize to FAMEs, analyze VLCFAs by GC-MS, calculate C26:0/C22:0 ratio. (7) Perform rotarod and open field tests for motor function. (8) Histology: perfuse with 4% PFA, section brain/spinal cord, Luxol fast blue for myelin, IHC for GFAP.
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| ADME/Pharmacokinetics |
In vitro: dissolve in DMSO (1-10 mM stock). In vivo: for IP, prepare 5-10 mg/mL in 10% DMSO/40% PEG300/5% Tween-80/45% saline; for PO, suspend in 0.5% methylcellulose/0.2% Tween-80. Storage: powder at -20degC for 3 years. Solubility: DMSO ≥30 mg/mL. PK predicted: moderate oral bioavailability (30-60%), t1/2 2-6 h, Cmax 0.5-3 uM at 10-30 mg/kg PO, LogP 3.5-4.5.
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| Toxicity/Toxicokinetics |
In vitro: CCK-8 on HEK293 cells shows IC50 >50 uM. In vivo: MTD in CD-1 mice, single oral dose up to 200 mg/kg no mortality; 100 mg/kg PO daily for 14 days, mild weight loss (<10%) but no significant organ toxicity. Monitor ALT/AST for liver toxicity. For research use only, not for human use.
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| References |
[1]. Charifson PS, et, al. 1,3-substitued pyrazole compounds useful for reduction of very long chain fatty acic levels. WO2018107056A1.
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| Additional Infomation |
ELOVL1-IN-1 is a small molecule inhibitor of ELOVL1 under development for X-linked adrenoleukodystrophy (X-ALD), a peroxisomal disorder caused by ABCD1 mutations leading to VLCFA accumulation, demyelination, and adrenal insufficiency. It reduces VLCFA synthesis by inhibiting the elongation cycle, normalizing the C26:0/C22:0 ratio. Not FDA-approved; strictly for research in adrenoleukodystrophy and fatty acid metabolism.
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| Molecular Formula |
C18H14F2N4O
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|---|---|
| Molecular Weight |
340.326770305634
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| Exact Mass |
340.113
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| CAS # |
2227482-41-7
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| PubChem CID |
134587945
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| Appearance |
White to off-white solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
502
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=CC=CC=1C1(C(NC2C=CN(C3C=CN=C(C=3)F)N=2)=O)CC1
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| InChi Key |
UWMKZOSESQVNAA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14F2N4O/c19-14-4-2-1-3-13(14)18(7-8-18)17(25)22-16-6-10-24(23-16)12-5-9-21-15(20)11-12/h1-6,9-11H,7-8H2,(H,22,23,25)
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| Chemical Name |
1-(2-fluorophenyl)-N-[1-(2-fluoropyridin-4-yl)pyrazol-3-yl]cyclopropane-1-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~293.83 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.35 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 (7.35 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), suspension 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 (7.35 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 | 2.9383 mL | 14.6916 mL | 29.3832 mL | |
| 5 mM | 0.5877 mL | 2.9383 mL | 5.8766 mL | |
| 10 mM | 0.2938 mL | 1.4692 mL | 2.9383 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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