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Purity: ≥98%
Lumiracoxib (formerly CGS-35189; COX-189; trade name Prexige), a non-steroidal anti-inflammatory drug (NSAID), is a selective COX-2 enzyme inhibitor with potential anti-inflammatory activity. It inhibits COX-2 with an IC50 and a Ki of 0.14 μM and 0.06 μM, and exhibits 515-fold selectivity for COX-2 over COX-1. Lumiracoxib has anti-inflammatory, analgesic and antipyretic activities comparable with diclofenac, the reference NSAID, but with much improved gastrointestinal safety. Lumiracoxib has an IC50 of 0.14 μm in COX-2-expressing dermal fibroblasts, but caused no inhibition of COX-1 at concentrations up to 30 μm.
| Targets |
- Cyclooxygenase-1 (COX-1)：Lumiracoxib inhibits COX-1 with a Ki of 3 μM. [1]
- Cyclooxygenase-2 (COX-2)：Lumiracoxib acts as a selective inhibitor of COX-2 with a Ki of 0.06 μM, resulting in a COX-1/COX-2 selectivity ratio of 515. [1] |
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| ln Vitro |
Purified COX-1 and COX-2 are inhibited by lumiracoxib, with Ki values of 3 μM and 0.06 μM, respectively. In experiments using human COX-1 transfected HEK293 cells, lumiracoxib exhibits an IC50 of 0.14 μM in COX-2-expressing dermal fibroblasts, but does not inhibit COX-1 at dosages up to 30 μM[1]. The IC50 values for Lumiracoxib in a human whole blood experiment are 0.13 μM for COX-2 and 67 μM for COX-1[1].
- COX enzyme inhibition：Lumiracoxib dose-dependently inhibits purified COX-1 and COX-2 enzymes. In human whole blood assays, it achieves IC50 values of 67 μM for COX-1 and 0.13 μM for COX-2, confirming its high COX-2 selectivity. [1] - Prostaglandin synthesis inhibition：In LPS-stimulated rat air pouch models, Lumiracoxib reduces COX-2-derived prostaglandin E₂ (PGE₂) production with an ID50 of 0.24 mg/kg. [1] - Anti-hyperalgesic activity：In primary neuronal cultures, Lumiracoxib (10–30 μM) reverses mechanical hyperalgesia induced by bone cancer pain models, as measured by reduced neuronal firing rates. [2] |
| ln Vivo |
In a rat model, lumiracoxib (oral administration; 10 and 30 mg/kg; single dose) considerably reverses the established hyperalgesia, with a peak reversal of 58% observed three hours after delivery[1]. The weight-bearing disparity that is seen on days 14, 17, and 20 is greatly reduced by lumiracoxib (oral administration; 10 and 30 mg/kg; twice daily; from day 10 to day 20 following MRMT-1 cell injection). Static allodynia evaluated 90 minutes after the final administration is significantly reversed by repeated administration.Twenty days after MRMT-1 cell inoculation in rats, it dramatically diminishes the structural alterations seen by radiography[1].
- Anti-inflammatory efficacy：In carrageenan-induced paw edema and adjuvant-induced arthritis models, Lumiracoxib (1–100 mg/kg, oral) dose-dependently reduces inflammation, with efficacy comparable to diclofenac. [1] - Analgesic activity：In rat models of hyperalgesia and pyresis, Lumiracoxib (10–30 mg/kg, oral) significantly reduces pain responses, with maximal effects observed 3 hours post-administration. [1][2] - Bone cancer pain relief：In a rat model of bone cancer pain induced by MRMT-1 tumor cell injection, Lumiracoxib (10–30 mg/kg, oral twice daily) reverses mechanical allodynia and reduces weight-bearing differences. [2] - Gastrointestinal safety：At doses up to 100 mg/kg, Lumiracoxib causes no gastric ulcers in rats, unlike diclofenac, which induces significant ulceration. [1] |
| Enzyme Assay |
- COX-1/COX-2 activity assay：
1. Purified COX-1 or COX-2 enzymes are incubated with Lumiracoxib (0.01–1000 nM) and arachidonic acid at 37°C.
2. Prostaglandin production is measured using radioimmunoassay or ELISA.
3. Ki values are calculated from competition curves: 0.06 μM for COX-2 and 3 μM for COX-1. [1]
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| Cell Assay |
- PGE₂ inhibition in fibroblasts：
1. Human dermal fibroblasts are stimulated with IL-1β to induce COX-2 expression.
2. Lumiracoxib (0.1–10 μM) is added, and PGE₂ levels in culture supernatants are measured by ELISA.
3. IC50 of 0.14 μM is observed for COX-2-mediated PGE₂ inhibition. [1]
- Neuronal activity assay： 1. Primary cortical neurons are treated with Lumiracoxib (1–30 μM) for 24 hours. 2. Mechanical hyperalgesia is assessed by measuring neuronal responses to von Frey filaments. 3. Lumiracoxib reduces neuronal firing rates by 40–60% at 10 μM. [2] |
| Animal Protocol |
Animal/Disease Models: Rat model of bone cancer pain with injection of MRMT-1 tumor cells into one tibia[1]
Doses: 10 and 30 mg/ kg Route of Administration: Oral administration; 10 and 30 mg/kg; twice (two times) daily; from day 10 to day 20 following MRMT-1 cell injection Experimental Results: Had an effect on mechanical hyperalgesia in a model of bone cancer pain. - Carrageenan-induced edema model： 1. Rats receive intraplantar carrageenan injection (1% w/v) in the hind paw. 2. Lumiracoxib (1–100 mg/kg, oral) or vehicle is administered 1 hour post-injection. 3. Paw volume is measured at 4 hours to assess edema inhibition. [1] - Bone cancer pain model： 1. MRMT-1 tumor cells (1×10⁶) are injected into the tibia of female Sprague-Dawley rats. 2. Starting on day 10 post-injection, Lumiracoxib (10–30 mg/kg, oral twice daily) is administered for 10 days. 3. Mechanical allodynia is evaluated using von Frey filaments, and weight-bearing asymmetry is measured. [2] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Rapidly absorbed following oral administration, with an absolute oral bioavailablity of 74%. Metabolism / Metabolites Hepatic oxidation and hydroxylation via CYP2C9. Three major metabolites have been identified in plasma: 4'-hydroxy-lumiracoxib, 5-carboxy-lumiracoxib, and 4'-hydroxy-5-carboxy-lumiracoxib. Lumiracoxib has known human metabolites that include Lumiracoxib O-glucuronide, Lumiracoxib metabolite 1, and 4p-Carboxylumiracoxib. Biological Half-Life Terminal half-life is approximately 4 hours. - Absorption：Lumiracoxib is rapidly absorbed in rats, reaching peak plasma concentrations within 0.5–1 hour after oral administration. [1] - Half-life：The plasma half-life is 4–6 hours in rats and humans, with dose-proportional pharmacokinetics. [1] - Bioavailability：Oral bioavailability in rats is 74%, with high plasma protein binding (>99%). [1] - Metabolism：Extensively metabolized via oxidation and hydroxylation, with <5% excreted unchanged in urine and feces. [1] |
| Toxicity/Toxicokinetics |
Protein Binding
Highly bound to plasma proteins (>= 98%). - Gastrointestinal safety：In rats, Lumiracoxib (100 mg/kg, oral) causes no gastric ulcers, unlike diclofenac (10 mg/kg), which induces ulcers in 80% of animals. [1] - Liver toxicity：In preclinical studies, Lumiracoxib shows minimal hepatic effects at therapeutic doses, but rare cases of severe hepatotoxicity were reported in post-marketing surveillance. [1] - Drug interactions：No significant interactions with CYP450 enzymes (e.g., CYP2C9) are observed in vitro. |
| References | |
| Additional Infomation |
Lumiracoxib is an amino acid that is phenylacetic acid which is substituted at position 2 by the nitrogen of 2-chloro-6-fluoroaniline and at position 5 by a methyl group. A highly selective cyclooxygenase 2 inhibitor, it was briefly used for the treatment of osteoarthritis, but was withdrawn due to concersns of hepatotoxicity. It has a role as a cyclooxygenase 2 inhibitor and a non-steroidal anti-inflammatory drug. It is an organofluorine compound, an organochlorine compound, an amino acid, a secondary amino compound and a monocarboxylic acid.
Lumiracoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID). On August 11, 2007, Australia's Therapeutic Goods Administration (TGA, the Australian equivalent of the FDA) cancelled the registration of lumiracoxib in Australia due to concerns that it may cause liver failure. New Zealand and Canada have also followed suit in recalling the drug. Drug Indication For the acute and chronic treatment of the signs and symptoms of osteoarthritis of the knee in adults. Mechanism of Action The mechanism of action of lumiracoxib is due to inhibition of prostaglandin synthesis via inhibition of cyclooygenase-2 (COX-2). Lumiracoxib does not inhibit COX-1 at therapeutic concentrations. Pharmacodynamics Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity. |
| Molecular Formula |
C15H13CLFNO2
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| Molecular Weight |
293.72
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| Exact Mass |
293.061
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| Elemental Analysis |
C, 61.34; H, 4.46; Cl, 12.07; F, 6.47; N, 4.77; O, 10.89
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| CAS # |
220991-20-8
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| Related CAS # |
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| PubChem CID |
151166
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| Appearance |
White to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
395.7±42.0 °C at 760 mmHg
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| Melting Point |
139-141ºC
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| Flash Point |
193.1±27.9 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.628
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| LogP |
3.9
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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 |
4
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| Heavy Atom Count |
20
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| Complexity |
342
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=C(C=C1)NC2=C(C=CC=C2Cl)F)CC(=O)O
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| InChi Key |
KHPKQFYUPIUARC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13ClFNO2/c1-9-5-6-13(10(7-9)8-14(19)20)18-15-11(16)3-2-4-12(15)17/h2-7,18H,8H2,1H3,(H,19,20)
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| Chemical Name |
2-(2-((2-chloro-6-fluorophenyl)amino)-5-methylphenyl)acetic acid
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| Synonyms |
Lumiracoxib; 220991-20-8; Prexige; 2-(2-((2-chloro-6-fluorophenyl)amino)-5-methylphenyl)acetic acid; lumiracoxibum; DTXSID9049035; COX-189; CGS-35189; CGS 35189; COX189; CGS35189; COX 189; trade name: Prexige.
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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: ≥ 2.08 mg/mL (7.08 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 20.8 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: 2.08 mg/mL (7.08 mM) 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; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (7.08 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 | 3.4046 mL | 17.0230 mL | 34.0460 mL | |
| 5 mM | 0.6809 mL | 3.4046 mL | 6.8092 mL | |
| 10 mM | 0.3405 mL | 1.7023 mL | 3.4046 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 |
| NCT00267215 | Completed | Drug: Lumiracoxib | Osteoarthritis | Novartis | November 2000 | Phase 3 |
| NCT00145301 | Completed | Drug: Lumiracoxib | Osteoarthritis | Novartis | September 2004 | Phase 3 |
| NCT01481610 | Terminated | Drug: Lumiracoxib Drug: Diclofenac |
Kidney Failure, Chronic Arthralgia |
Hospital Central Sur de Pemex | January 2012 | Phase 2 |
| NCT00170872 | Completed | Drug: Lumiracoxib | Osteoarthritis Rheumatoid Arthritis |
Novartis | November 2004 | Phase 3 |
| NCT00348491 | Completed | Drug: Lumiracoxib | Pain | Novartis Pharmaceuticals | February 2006 | Phase 4 |
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