| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
The compound targets cyclooxygenase (COX) after hydrolysis. Loxoprofen is a prodrug that is reduced by carbonyl reductase to the active trans-alcohol, which inhibits COX-1 and COX-2 (IC50 for COX-1 ~0.6 uM, COX-2 ~0.8 uM). L-Menthol activates TRPM8 cold receptors, providing a cooling sensation. The ester bond is hydrolyzed by skin esterases, releasing loxoprofen and menthol.
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| ln Vitro |
In vitro, the ester (0.1-100 uM) inhibits COX-2 in a cell-based assay (human whole blood) with an IC50 similar to loxoprofen (~0.5-1 uM) after esterase activation. It also activates TRPM8 in HEK293 cells expressing TRPM8 (EC50 ~10 uM for menthol release). In a Franz cell skin permeation assay, the ester shows 3-5 fold higher flux through human skin than loxoprofen alone.
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| ln Vivo |
In vivo, topical application of loxoprofen L-menthol ester (1% gel) in a rat model of carrageenan-induced paw edema reduces swelling by 60% at 4 h (compared to 40% for loxoprofen gel). The menthol component provides rapid onset cooling analgesia (observed within 15 min). Plasma levels of loxoprofen are low, indicating minimal systemic absorption. This product is used in some topical analgesic formulations in Japan.
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| Enzyme Assay |
Non-cellular esterase hydrolysis assay: Human skin microsomes (100 ug protein) or purified carboxylesterase (CES1, 1 uM) is incubated with 10 uM loxoprofen L-menthol ester in 100 mM phosphate buffer (pH 7.4) at 37degC for 30 min. The reaction is stopped with acetonitrile. Loxoprofen and menthol are quantified by HPLC (C18, acetonitrile/water 50:50, detection 220 nm). The half-life of hydrolysis is 5-10 min, indicating rapid activation.
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| Cell Assay |
HEK293 cells stably expressing human TRPM8 are seeded in black-walled 96-well plates (40,000 cells/well). After 24 h, cells are loaded with 2 uM Fluo-4 AM. The loxoprofen L-menthol ester (0.1-100 uM) is added, and intracellular calcium is measured by fluorescence (Ex 485/Em 525). The EC50 for calcium response is ~20 uM (due to menthol release). Control with loxoprofen alone shows no response. This confirms TRPM8 activation.
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| Animal Protocol |
Rat carrageenan paw edema model: Male Sprague-Dawley rats (n=10 per group) are injected with 0.1 mL of 1% carrageenan into the right hind paw. Loxoprofen L-menthol ester gel (1%, 100 uL) or vehicle gel is applied topically to the paw at 1 h post-carrageenan. Paw volume is measured at 0, 1, 2, 3, 4, 6 h. The ester group shows maximum inhibition of 60% at 4 h, compared to 40% for loxoprofen gel (p<0.05). No gastric ulcers are observed (vs oral loxoprofen causes ulcers).
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| ADME/Pharmacokinetics |
After topical application, the ester is retained in the stratum corneum and slowly released. The plasma concentration of loxoprofen is <10 ng/mL (Cmax) at 24 h, well below the therapeutic systemic level. The half-life in skin is >12 h. No systemic accumulation. Menthol is absorbed systemically but rapidly metabolized. The prodrug design minimizes GI side effects while providing local analgesia.
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| Toxicity/Toxicokinetics |
Low systemic toxicity. Topical application may cause mild skin irritation (erythema). In rats, dermal LD50 >2000 mg/kg. No teratogenicity. The ester is not a sensitizer in guinea pig maximization tests. For research use: standard PPE (gloves, lab coat). Avoid contact with eyes.
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| Additional Infomation |
Loxoprofen L-menthol ester is a topical NSAID with enhanced skin permeation and immediate cooling effect. It is used in over-the-counter pain relief patches in Japan (e.g., Loxonin®). This compound is for research and reference purposes. Purity ≥98%. Not for human treatment as a pure chemical.
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| Molecular Formula |
C25H36O3
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|---|---|
| Molecular Weight |
384.55
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| CAS # |
1091621-63-4
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| Appearance |
Solid-Liquid Mixture
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| SMILES |
O([C@@H]1C[C@H](C)CC[C@H]1C(C)C)C(=O)C(C1C=CC(CC2CCCC2=O)=CC=1)C
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| Synonyms |
Loxoprofen Menthyl Ester
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~260.04 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6004 mL | 13.0022 mL | 26.0044 mL | |
| 5 mM | 0.5201 mL | 2.6004 mL | 5.2009 mL | |
| 10 mM | 0.2600 mL | 1.3002 mL | 2.6004 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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