| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
15-LOX-1 0.19 μM (IC50)
15-LOX-1 inhibitor 1 selectively targets the 15-lipoxygenase-1 (15-LOX-1) enzyme. It is a potent inhibitor, exhibiting a biochemical IC50 of 0.19 microM. The enzyme 15-LOX-1 is involved in the production of various eicosanoids and specialized pro-resolving mediators (SPMs) from arachidonic acid and linoleic acid. By blocking this enzyme, the compound helps researchers dissect its specific contribution to inflammatory signaling and disease pathology. |
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| ln Vitro |
Compound 9c, also known as 15-LOX-1 inhibitor 1 (0-5 μM; 24 hours) has dose-dependent effects that are more pronounced and result in a 20% increase in survivability for RAW 264.7 macrophages when exposed to LPS[1].
In vitro, 15-LOX-1 inhibitor 1 is a potent inhibitor of 15-LOX-1 with an IC50 value of 0.19 uM. More importantly, it protects macrophages from lipopolysaccharide (LPS)-induced cytotoxicity. At a concentration of 5 uM, treatment with this inhibitor leads to a 20% increase in RAW 264.7 macrophage viability following an LPS challenge, demonstrating a dose-dependent protective effect. This cytoprotective activity suggests that 15-LOX-1 plays a role in LPS-induced cell death. |
| ln Vivo |
Published in vivo activity data for 15-LOX-1 inhibitor 1 is not detailed in the provided sources. However, due to its potent ability to protect macrophages from inflammatory death in vitro, it is hypothesized to have therapeutic potential in animal models of acute and chronic inflammation. It could be tested in models of LPS-induced sepsis, acute lung injury, or colitis to evaluate its capacity to reduce tissue damage and inflammatory cytokine production.
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| Enzyme Assay |
The in vitro potency of 15-LOX-1 inhibitor 1 is determined using a cell-free enzyme activity assay. Recombinant human 15-LOX-1 enzyme is incubated in an assay buffer with varying concentrations of the inhibitor (e.g., 0.001-100 microM). The reaction is initiated by the addition of the substrate, typically linoleic acid. After a short incubation, the reaction is quenched, and the product (13-HPODE) is extracted and quantified by HPLC or by measuring the absorbance at 234 nm. The concentration causing 50% inhibition (IC50) is calculated (0.19 microM).
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: RAW 264.7 macrophages Tested Concentrations: 0, 0.2, 1, 5 μM 15-LOX-1 inhibitor 1 and lipopolysaccharides (LPS) (100 μg/mL) Incubation Duration: 24 hrs (hours) Experimental Results: demonstrated stronger , dose-dependent effects with a 20% viability increase at 5 μM. For cellular assays, RAW 264.7 murine macrophages are seeded in 96-well plates. The cells are pre-incubated with 15-LOX-1 inhibitor 1 at concentrations ranging from 0-5 microM for 1 hour. Inflammation and cytotoxicity are then induced by the addition of lipopolysaccharide (LPS, e.g., 1 ug/mL) for 24 hours. Cell viability is assessed using the MTT assay. The protective effect of the inhibitor is quantified as the percentage of viable cells compared to an LPS-treated, inhibitor-free control group. An LDH release assay can also be performed to measure cell death. |
| Animal Protocol |
In vivo studies with 15-LOX-1 inhibitor 1 could be performed using a mouse model of acute inflammation induced by lipopolysaccharide (LPS). The compound would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline). Mice would be administered the compound via intraperitoneal injection at various doses (e.g., 1-20 mg/kg) 1-2 hours prior to an LPS challenge (e.g., 10-20 mg/kg, i.p.). Blood and tissue samples (liver, lung) would be collected 6-24 hours post-LPS to measure serum cytokine levels (e.g., TNF-alpha, IL-1beta, IL-6) by ELISA and organ damage by histology and serum alanine aminotransferase (ALT) levels.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for 15-LOX-1 inhibitor 1 is not publicly available. The compound has a molecular weight of 412.87 g/mol. Based on its structure, it is likely to be lipophilic. For in vivo studies, it would need to be formulated using a co-solvent system like DMSO, PEG300, and saline to achieve adequate solubility. Researchers would need to conduct pilot PK studies to determine its half-life, Cmax, and bioavailability in their specific animal model.
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| Toxicity/Toxicokinetics |
Publicly available toxicology data for 15-LOX-1 inhibitor 1 is limited. In cell-based assays, concentrations up to 5 uM are used to demonstrate cytoprotection without overt cytotoxicity, as measured by the MTT assay. In these experiments, the inhibitor increases viability, suggesting a lack of intrinsic toxicity at these concentrations. For any animal study, standard safety assessments would be required.
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| References | |
| Additional Infomation |
15-LOX-1 inhibitor 1 is a research-grade compound and is not approved for clinical use. It is a valuable and potent tool compound for investigating the biological role of the 15-LOX-1 enzyme in inflammation and immunity. Its cytoprotective effects in macrophages make it particularly useful for studying the mechanisms of inflammatory cell death. The compound should be stored at -20degC as a powder, protected from light and moisture. For research use only.
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| Molecular Formula |
C22H21CLN2O4
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|---|---|
| Molecular Weight |
412.87
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| Exact Mass |
412.118
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| CAS # |
2349374-37-2
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| PubChem CID |
145874872
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
683.5±55.0 °C at 760 mmHg
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| Flash Point |
367.2±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
4.74
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
29
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| Complexity |
599
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=C(C2=C(N1)C=C(C=C2)Cl)/C=C/C(=O)NCC3=CC=CC=C3OC
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| InChi Key |
BRMZRDPEXXAZRV-ZHACJKMWSA-N
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| InChi Code |
InChI=1S/C22H21ClN2O4/c1-3-29-22(27)21-17(16-9-8-15(23)12-18(16)25-21)10-11-20(26)24-13-14-6-4-5-7-19(14)28-2/h4-12,25H,3,13H2,1-2H3,(H,24,26)/b11-10+
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| Chemical Name |
ethyl 6-chloro-3-[(E)-3-[(2-methoxyphenyl)methylamino]-3-oxoprop-1-enyl]-1H-indole-2-carboxylate
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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 |
| 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: 10 mg/mL (24.22 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4221 mL | 12.1103 mL | 24.2207 mL | |
| 5 mM | 0.4844 mL | 2.4221 mL | 4.8441 mL | |
| 10 mM | 0.2422 mL | 1.2110 mL | 2.4221 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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