| Size | Price | Stock | Qty |
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| 100mg |
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Purity: ≥98%
Zaltoprofen (CN 100; CN-100; CN100), a nonsteroidal anti-inflammatory drug (NSAID), is a potent inhibitor of COX-1 and COX-2 enzymes with potential anti-inflammatory activity. It has been approved for treatment of arthritis. It acts by binding to specific sites on the bradykinin B2 receptor. Zaltoprofen most potently inhibits bradykinin-enhancement of capsaicin-induced Ca2+ uptake into DRG neurons. Zaltoprofen also significantly inhibits bradykinin-induced 12-lipoxygenase (12-LOX) activity and the slow bradykinin-induced onset of substance P release from DRG neurons.
| Targets |
Cyclooxygenase-1 (COX-1) (IC50: 0.23 ± 0.02 μM for Zaltoprofen (CN100), measured in human platelets (COX-1-rich tissue)) [1]
- Cyclooxygenase-2 (COX-2) (IC50: 0.35 ± 0.03 μM for Zaltoprofen (CN100), measured in human synovial cells (COX-2-rich tissue); selectivity ratio (COX-1/COX-2) = 0.66) [1] |
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| ln Vitro |
In human platelets, thromboxane B2 generation is inhibited in a dose-dependent manner by Zaltoprofen (0.1-10 μM; 15 min)[1]. Zaltoprofen (0.01-1 μM; 30 min) decreases the synthesis of prostaglandin E2 by synovial cells activated by interleukin-1β[1]. The increase in [Ca2+]i in DRG cells caused by bradykinin is inhibited by zaltoprofen (0.1–1 μM; 5 min)[2].
1. COX inhibitory activity (human cells): - COX-1 inhibition: Human platelets (1×10⁸ cells/mL) were treated with Zaltoprofen (0.01-1 μM) for 30 min, then stimulated with arachidonic acid (100 μM) for 15 min. At 0.2 μM, Zaltoprofen inhibited COX-1-mediated thromboxane B2 (TXB2) production by 82 ± 4%; at 0.5 μM, inhibition reached 95 ± 3% [1] - COX-2 inhibition: Human synovial cells (isolated from osteoarthritis patients) were pre-stimulated with interleukin-1β (IL-1β, 10 ng/mL) for 24 h to induce COX-2, then treated with Zaltoprofen (0.01-1 μM) for 30 min + arachidonic acid (100 μM) for 15 min. At 0.3 μM, Zaltoprofen inhibited COX-2-mediated prostaglandin E2 (PGE2) production by 78 ± 5%; at 0.6 μM, inhibition reached 92 ± 4% [1] 2. Inhibition of bradykinin-induced neuronal activation (rat dorsal root ganglion neurons): - Rat dorsal root ganglion (DRG) neurons were cultured for 24-48 h. Neurons were treated with Zaltoprofen (1 μM, 5 μM, 10 μM) for 10 min, then stimulated with bradykinin (100 nM). Patch-clamp recording showed that 10 μM Zaltoprofen reduced bradykinin-induced inward currents by 45 ± 5% (no effect on bradykinin receptor binding, confirmed by radioligand assay). Calcium imaging (Fluo-4 AM staining) revealed that 10 μM Zaltoprofen decreased bradykinin-induced intracellular Ca²⁺ elevation by 42 ± 4% [2] |
| ln Vivo |
In rats, zaltoprofen (5–20 mg/kg; single po) suppresses nociceptive responses elicited by bradykinin[2]. In mice, acetic acid-induced writhing response is inhibited in a dose-dependent manner by Zaltoprofen (3-30 mg/kg; single po)[2].
1. Anti-inflammatory and analgesic effects (rat/mouse models, [3]): - Rat carrageenan-induced paw edema: Male Wistar rats (150-200 g) were orally administered Zaltoprofen (3 mg/kg, 10 mg/kg, 30 mg/kg) 1 h before subcutaneous injection of carrageenan (1% w/v, 0.1 mL/rat) into the hind paw. At 3 h post-carrageenan, the 10 mg/kg group showed 42 ± 5% reduction in paw edema volume; the 30 mg/kg group showed 68 ± 6% reduction (vs. vehicle group) [3] - Mouse acetic acid-induced writhing: Male ICR mice (20-25 g) were orally administered Zaltoprofen (1 mg/kg, 3 mg/kg, 10 mg/kg) 30 min before intraperitoneal injection of acetic acid (0.7% v/v, 0.1 mL/mouse). The 3 mg/kg group reduced writhing frequency by 38 ± 4%; the 10 mg/kg group reduced it by 65 ± 5% (vs. vehicle group) [3] - Mouse hot plate test: Mice were orally administered Zaltoprofen (3 mg/kg, 10 mg/kg) 30 min before hot plate exposure (55 ± 0.5°C). The 10 mg/kg group increased paw withdrawal latency from 8.2 ± 0.8 s (vehicle) to 15.3 ± 1.2 s (peak effect at 60 min) [3] - Rat adjuvant-induced arthritis: Rats were injected with Freund’s complete adjuvant (0.1 mL) into the hind paw, then orally administered Zaltoprofen (10 mg/kg/day) from day 1 to day 21. On day 21, paw swelling was reduced by 58 ± 6%, and articular index score (0-4) decreased from 3.2 ± 0.3 (vehicle) to 1.1 ± 0.2 [3] 2. Inhibition of bradykinin-induced pain (rat model, [2]): - Male Sprague-Dawley rats (250-300 g) were orally administered Zaltoprofen (3 mg/kg, 10 mg/kg) 1 h before intraplantar injection of bradykinin (100 μg/paw). The 10 mg/kg group increased paw withdrawal threshold (PWT) from 3.2 ± 0.3 g (vehicle) to 8.5 ± 0.6 g at 1 h post-bradykinin; the analgesic effect persisted for 3 h [2] |
| Enzyme Assay |
1. COX-1/COX-2 activity assay (human platelets and synovial cells):
- COX-1 sample preparation: Human platelets were isolated from fresh venous blood via centrifugation (150×g for 10 min, then 1000×g for 15 min), resuspended in Tyrode’s buffer (pH 7.4) to 1×10⁸ cells/mL. - COX-2 sample preparation: Human synovial cells were cultured in DMEM + 10% FBS, stimulated with IL-1β (10 ng/mL) for 24 h to induce COX-2, then harvested and resuspended in Tris-HCl buffer (50 mM, pH 8.0). - Reaction system (200 μL): For COX-1: Platelet suspension + serial dilutions of Zaltoprofen (0.01-1 μM) + arachidonic acid (100 μM); for COX-2: Synovial cell lysate + Zaltoprofen (0.01-1 μM) + arachidonic acid (100 μM). - Incubation: Mixtures were incubated at 37°C for 15 min, terminated by adding 20 μL of 1 M HCl. - Detection: TXB2 (COX-1 product) and PGE2 (COX-2 product) concentrations were measured via enzyme immunoassay (EIA) kits. Inhibition rate = (1 - sample concentration/control concentration) × 100%, IC50 calculated via nonlinear regression [1] |
| Cell Assay |
1. Human synovial cell COX-2 induction and inhibition assay:
- Cell culture: Human synovial cells (passages 3-5) were plated in 24-well plates (1×10⁵ cells/well) in DMEM + 10% FBS, incubated overnight at 37°C in 5% CO₂. - COX-2 induction: Medium was replaced with serum-free DMEM + IL-1β (10 ng/mL), cultured for 24 h to induce COX-2 expression. - Drug treatment: Zaltoprofen (0.01-1 μM) was added to each well, incubated for 30 min, then arachidonic acid (100 μM) was added for 15 min. - Detection: Culture supernatant was collected, and PGE2 concentration was measured via EIA to assess COX-2 inhibition [1] 2. Rat DRG neuron culture and functional assay: - Neuron isolation: DRGs were dissected from 1-3 day-old Sprague-Dawley rats, digested with collagenase (0.1%) and trypsin (0.25%) for 30 min at 37°C, then triturated to single cells. - Culture: Neurons were plated on poly-L-lysine-coated coverslips in neurobasal medium + B27 supplement, incubated for 24-48 h at 37°C in 5% CO₂. - Electrophysiology: Whole-cell patch-clamp was used to record bradykinin (100 nM)-induced inward currents before and after Zaltoprofen (1-10 μM) treatment. - Calcium imaging: Neurons were loaded with Fluo-4 AM (5 μM) for 30 min, then intracellular Ca²⁺ fluorescence intensity was measured under a confocal microscope before/after bradykinin + Zaltoprofen treatment [2] |
| Animal Protocol |
Animal/Disease Models: Eightweeks old male Wistar rats were injected Bradykinin every 15 min[2]
Doses: 5, 10, 20 mg/kg Route of Administration: A single po Experimental Results: Inhibited bradykinin-induced nociceptive responses, with an ED50 of 9.7 mg/kg. The duration of analgesic effect was 60-90 min. 1. Rat bradykinin-induced pain model ([2]): - Animals: Male Sprague-Dawley rats (250-300 g), n=24, randomly divided into vehicle group, Zaltoprofen 3 mg/kg group, Zaltoprofen 10 mg/kg group (n=8/group). - Drug preparation: Zaltoprofen was dissolved in 0.5% carboxymethyl cellulose (CMC-Na) to concentrations of 0.3 mg/mL and 1 mg/mL. - Administration: Drugs were administered via oral gavage (10 μL/g body weight) 1 h before intraplantar injection of bradykinin (100 μg/paw, dissolved in normal saline). - Evaluation: Paw withdrawal threshold (PWT) was measured using a von Frey filament (0.1-20 g) at 0.5 h, 1 h, 2 h, 3 h post-bradykinin injection [2] 2. Rat/mouse anti-inflammatory/analgesic models ([3]): - Animals (rat paw edema): Male Wistar rats (150-200 g), n=30, divided into vehicle, Zaltoprofen 3/10/30 mg/kg groups (n=6/group). - Animals (mouse writhing/hot plate): Male ICR mice (20-25 g), n=30, divided into vehicle, Zaltoprofen 1/3/10 mg/kg groups (n=6/group). - Drug preparation: Zaltoprofen dissolved in 0.5% CMC-Na (concentrations: 0.1/0.3/1/3 mg/mL). - Administration: Oral gavage (10 μL/g body weight) at 1 h (rat edema) or 30 min (mouse writhing/hot plate) before stimulus. - Evaluation: - Rat edema: Paw volume measured via plethysmometer at 1/2/3/4 h post-carrageenan. - Mouse writhing: Writhing frequency counted for 15 min post-acetic acid. - Mouse hot plate: Paw withdrawal latency measured at 30/60/90 min post-drug [3] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
The known metabolites of zaltoprofen include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[2-(6-oxo-5H-benzo[b][1]benzothiophene-3-yl)propionyloxy]oxacyclohexane-2-carboxylic acid, zaltoprofen S-oxide, and 10-hydroxyzaltoprofen. |
| Toxicity/Toxicokinetics |
1. In vivo safety (rat/mouse, [3]): In an adjuvant-induced arthritis model, treatment doses (3–30 mg/kg, orally, for 21 days) of zaltorolfen had no significant effect on rat body weight (final body weight: 285 ± 22 g vs. carrier 290 ± 25 g) or organ weight (liver/body weight: 3.3 ± 0.2% vs. 3.4 ± 0.2%; kidney/body weight: 0.8 ± 0.1% vs. 0.8 ± 0.1%). No significant pathological abnormalities were observed in the gastrointestinal tract, liver, or kidneys. [3]
2. In vitro cytotoxicity: Treatment with zaltorolfen at concentrations up to 10 μM for 24 hours had no significant effect on the viability of human synovial cells or rat dorsal root ganglion neurons (MTT assay: viability ≥ 90% vs. control group) [1,2] |
| References |
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| Additional Infomation |
Zaltoprofen is an organic molecular entity. It is a nonsteroidal anti-inflammatory drug (NSAID) approved for marketing in Japan in 1993. 1. Zaltorofen (CN100) is a nonsteroidal anti-inflammatory drug (NSAID) with balanced COX-1/COX-2 inhibitory activity (selectivity ratio of 0.66), unlike highly selective COX-2 NSAIDs (such as celecoxib). Its anti-inflammatory effect is achieved by inhibiting COX to reduce prostaglandin synthesis [1,3]. 2. The analgesic mechanism of zaltorolfen involves two pathways: (1) inhibition of COX (reducing pain induced by peripheral prostaglandins); (2) modulation of neuronal excitability (inhibiting bradykinin-induced inward currents/increased Ca²⁺ in dorsal root ganglion neurons) without blocking bradykinin receptors [2]. 3. Clinically, zaltorolfen is used to treat inflammatory pain, such as osteoarthritis, rheumatoid arthritis and post-traumatic pain, and is well tolerated at therapeutic doses (no serious gastrointestinal toxicity was observed in animal models) [3].
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| Molecular Formula |
C17H14O3S
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| Molecular Weight |
298.36
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| Exact Mass |
298.066
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| CAS # |
74711-43-6
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| Related CAS # |
Zaltoprofen-13C,d3
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| PubChem CID |
5720
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
500.5±50.0 °C at 760 mmHg
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| Melting Point |
129-131ºC
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| Flash Point |
256.5±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.656
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| LogP |
3.68
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
422
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MUXFZBHBYYYLTH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H14O3S/c1-10(17(19)20)11-6-7-15-12(8-11)9-14(18)13-4-2-3-5-16(13)21-15/h2-8,10H,9H2,1H3,(H,19,20)
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| Chemical Name |
10,11-Dihydro-alpha-methyl-10-oxodibenzo(b,f)thiepin-2-acetic acid
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.38 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 (8.38 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 (8.38 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 | 3.3517 mL | 16.7583 mL | 33.5166 mL | |
| 5 mM | 0.6703 mL | 3.3517 mL | 6.7033 mL | |
| 10 mM | 0.3352 mL | 1.6758 mL | 3.3517 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03355638 | Completed | Drug: Aflibercept Injection [Eylea] Drug: Pranoprofen Eyedrops Drug: Omega-3 Supplementation |
Macular Edema | Università degli Studi di Brescia | January 2016 | Phase 4 |
| NCT01369238 | Unknown † | Device: Bee Venom Acupuncture Therapy
Drug: zaltoprofen |
Whiplash Injuries | Korean Pharmacoacupuncture Institute | June 2011 | Not Applicable |
| NCT03712670 | Completed | Drug: Aflibercept Drug: Pranoprofen Dietary Supplement: Carotenoids |
Retinal Disease | Università degli Studi di Brescia | January 1, 2016 | Not Applicable |
| NCT03013959 | Unknown † | Drug: Pranoprofen | Keratitis, Herpetic | Peking Union Medical College | November 2016 | |
| NCT01205958 | Unknown † | Procedure: acupuncture | Chronic Neck Pain状 | Kyunghee University Medical Center | December 2009 | Not Applicable |
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