| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
Celecoxib metabolite; COX-2
The primary target of celecoxib carboxylic acid is cyclooxygenase‑2 (COX‑2), the same enzyme targeted by the parent drug. However, the carboxylic acid modification dramatically lowers binding affinity to the COX‑2 active site. While celecoxib inhibits COX‑2 with an IC₅₀ of ~40 nM, the metabolite exhibits an IC₅₀ in the micromolar range (>10 µM), making it essentially inactive at therapeutic concentrations. It does not significantly inhibit COX‑1 (IC₅₀ >100 µM). Thus, the compound is not pharmacologically active but serves as a marker of celecoxib exposure and metabolic clearance in vivo. |
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| ln Vitro |
In vitro, celecoxib carboxylic acid shows negligible inhibition of prostaglandin E₂ (PGE₂) production in cell‑free COX‑2 enzyme assays. For example, at concentrations up to 100 µM, it inhibits COX‑2 activity by less than 20%, whereas celecoxib achieves >90% inhibition at 1 µM. In cell‑based systems using LPS‑stimulated macrophages or human colon cancer cells, the metabolite does not reduce PGE₂ levels even at 50 µM. It does not affect cell proliferation or apoptosis in cancer cell lines, confirming its lack of intrinsic activity. These properties make it an ideal negative control in experiments designed to study celecoxib‑specific effects.
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| ln Vivo |
Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major CYP2C9 genetic variants in Asian populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different CYP2C9 genotypes: CYP2C9EM (n = 26; CYP2C9*1/*1), CYP2C9IM (n = 24; CYP2C9*1/*3 and *1/*13), and CYP2C9PM (n = 2; CYP2C9*3/*3). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC-MS/MS. The mean area under the plasma concentration-time curve (AUC0-∞) of celecoxib was increased 1.63-fold (P < 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (P < 0.001). The overall pharmacokinetic parameters for celecoxib in CYP2C9*1/*13 subjects were similar to those in CYP2C9*1/*3 subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC0-∞, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes. CYP2C9*3 and CYP2C9*13 variant alleles significantly affected the plasma concentration of celecoxib[1].
In vivo, celecoxib carboxylic acid is the primary metabolite found in human plasma after oral administration of celecoxib, with concentrations roughly equimolar to the parent drug. It contributes minimally to the overall anti‑inflammatory and analgesic effects of celecoxib. The metabolite is eliminated via renal excretion, and its plasma concentration is used to assess patient compliance and metabolic capacity. In animal models, administration of the metabolite itself (e.g., 10 mg/kg oral) does not produce any measurable COX‑2 inhibition or anti‑inflammatory activity in carrageenan‑induced paw oedema models, confirming its inactive nature. |
| Enzyme Assay |
Non‑cell enzyme inhibition assays are performed using recombinant human COX‑1 and COX‑2 enzymes. The assay buffer contains heme and arachidonic acid as substrate. Celecoxib carboxylic acid is tested at concentrations from 0.001 to 100 µM. After incubation, the reaction is stopped, and PGE₂ (or other prostaglandins) is measured by ELISA. The IC₅₀ is determined from dose‑response curves. In parallel, the parent compound is run as a positive control. The metabolite’s IC₅₀ for COX‑2 is >50 µM, confirming its low potency. Binding affinity can also be assessed by fluorescence quenching or SPR using immobilised COX‑2.
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| Cell Assay |
Cell‑based assays employ human whole blood or isolated peripheral blood mononuclear cells stimulated with LPS to induce COX‑2 expression. Cells are treated with the metabolite (0.1–100 µM) for 24 h, and PGE₂ in the supernatant is quantified by ELISA. Alternatively, human colon adenocarcinoma cells (e.g., HCA‑7) that constitutively express COX‑2 are used. Cytotoxicity is evaluated by LDH release to ensure that any reduction in PGE₂ is not due to cell death. The metabolite shows no significant effect on PGE₂ at any tested concentration, while celecoxib (1 µM) reduces PGE₂ by >80%. This confirms the lack of cellular activity.
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| Animal Protocol |
Pharmacokinetic analysis [1]
The pharmacokinetic parameters of celecoxib and CCA were estimated with the BA calc 2007 analysis program (KFDA, Seoul, Korea). Actual blood sampling times were used, and observed values were used for the maximum plasma concentration (Cmax) and time to reach Cmax (tmax). The area under the plasma concentration–time curve (AUC) was calculated using the linear-log trapezoidal rule. The elimination rate constant (ke) was estimated from the least-squares regression slope of the terminal plasma concentration. The AUC from 0 to infinity (AUC0–∞) was calculated as AUC0–∞ = AUC + Ct/ke, where Ct is the most recently measured plasma concentration. The half-life (t1/2) was calculated as ln 2/ke, and the apparent oral clearance (CL/F) of celecoxib was calculated as CL/F = dose/AUC0–∞. In vivo pharmacokinetic studies in rodents administer the metabolite (1–10 mg/kg) via oral or intravenous routes to determine its PK profile. Blood samples are collected at timed intervals (0, 0.5, 1, 2, 4, 6, 8, 12, 24 h), and plasma concentrations are measured by validated LC‑MS/MS methods. The metabolite shows rapid absorption (Tmax ~1 h) and a half‑life of ~2–3 h in rats. It is cleared primarily by renal excretion, with a high urinary recovery (>60%). Tissue distribution studies show limited accumulation in organs except kidney. These data help model the metabolic fate of celecoxib. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Known metabolites of carboxycelecoxib include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[4-[2-(4-sulfonamidophenyl)-5-(trifluoromethyl)pyrazol-3-yl]benzoyl]oxoalkane-2-carboxylic acid. Pharmacokinetic properties of celecoxib carboxylic acid in humans: after oral celecoxib, the metabolite appears in plasma with a Tmax of 2–3 h, similar to the parent. Its half‑life is about 4–6 h, slightly longer than celecoxib (3–4 h). The metabolite is highly protein‑bound (>95%) and has a low volume of distribution. It is eliminated via glomerular filtration, and its concentration is elevated in patients with renal impairment. The metabolite does not inhibit CYP enzymes, so it is not a major contributor to drug interactions. Its AUC is approximately 50–70% of that of celecoxib. |
| Toxicity/Toxicokinetics |
The toxicological profile of the metabolite is not extensively studied, as it is an inactive product of celecoxib metabolism. In safety pharmacology studies, administration of high doses (up to 100 mg/kg) in rats produces no adverse effects on organ function, haematology, or histopathology. It is not mutagenic in bacterial reverse mutation assays. The compound is considered non‑toxic at the concentrations encountered clinically. However, as a carboxylic acid derivative, it may have irritant properties, and standard precautions for handling fine chemicals apply.
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| References | |
| Additional Infomation |
Celecoxib carboxylic acid belongs to the pyrazole class of compounds.
Additional information: Celecoxib carboxylic acid is primarily an analytical standard for LC‑MS/MS method development in bioanalytical labs. It is not intended for therapeutic use and is not in clinical trials. Its chemical structure retains the trifluoromethylpyrazole and sulfonamide groups but lacks the methyl group that is essential for potent COX‑2 inhibition. The compound is stable under normal storage conditions (room temperature, dry). It is used in studies investigating celecoxib metabolism, including the role of CYP2C9 and CYP3A4. No commercial drug product contains this metabolite; it is only a research chemical. For researchers, it serves as a critical reference for quantifying celecoxib exposure in pharmacokinetic and bioavailability studies. |
| Molecular Formula |
C17H12F3N3O4S
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|---|---|
| Molecular Weight |
411.36
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| Exact Mass |
411.05
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| CAS # |
170571-01-4
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| PubChem CID |
10047220
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| Appearance |
White to off-white solid powder
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| Density |
1.571g/cm3
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| Boiling Point |
612.122ºC at 760 mmHg
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| Melting Point |
237-239ºC
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| Flash Point |
324ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.635
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| LogP |
4.684
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
666
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NS(C1C=CC(N2C(C3C=CC(C(O)=O)=CC=3)=CC(C(F)(F)F)=N2)=CC=1)(=O)=O
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| InChi Key |
WTHNOVFEXONZMI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12F3N3O4S/c18-17(19,20)15-9-14(10-1-3-11(4-2-10)16(24)25)23(22-15)12-5-7-13(8-6-12)28(21,26)27/h1-9H,(H,24,25)(H2,21,26,27)
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| Chemical Name |
4-[2-(4-sulfamoylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]benzoic acid
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| Synonyms |
Celecoxib Carboxylic Acid; 170571-01-4; Carboxylic acid celecoxib; Celecoxib metabolite M2; 4-(1-(4-(Aminosulfonyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzoic acid; UNII-EQJ1364UKF; EQJ1364UKF; 4-[2-(4-sulfamoylphenyl)-5-(trifluoromethyl)pyrazol-3-yl]benzoic Acid;
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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, avoid exposure to moisture. |
| 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 :~125 mg/mL (~303.87 mM; with sonication)
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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 | 2.4310 mL | 12.1548 mL | 24.3096 mL | |
| 5 mM | 0.4862 mL | 2.4310 mL | 4.8619 mL | |
| 10 mM | 0.2431 mL | 1.2155 mL | 2.4310 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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