COX-2 (IC50 = 40 nM); COX-1 (IC50 = 15 μM); non-steroidal anti-inflammatory drug (NSAID)
Celecoxib (SC 58635) is a selective cyclooxygenase-2 (COX-2) inhibitor. In in vitro enzyme assays, it exhibited high selectivity for human recombinant COX-2 with an IC₅₀ of 0.04 μM, while showing minimal inhibition of human COX-1 (IC₅₀ > 10 μM) and ovine COX-1 (IC₅₀ > 20 μM) [1]
- In nasopharyngeal carcinoma (NPC) cells, Celecoxib targets signal transducer and activator of transcription 3 (STAT3) by inhibiting its phosphorylation (p-STAT3), with no reported Ki/IC₅₀ values for direct STAT3 binding [2]
- In ovarian cancer cells, Celecoxib downregulates the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-TEAD oncogenic pathway, suppressing TEAD transcriptional activity [3, 6]

Celecoxib (10-75 μM), a selective cyclooxygenase-2 (COX-2) inhibitor, suppresses nasopharyngeal cancer cell line proliferation in a dose-dependent manner. In NPC cell lines, celecoxib (25 and 50 μM) caused apoptosis and cell cycle arrest at the G0/G1 checkpoint, which was linked to a notable reduction in STAT3 phosphorylation. Genes downstream of STAT3, including Survivin, Mcl-1, Bcl-2, and Cyclin D1, were markedly downregulated following exposure to Celecoxib (25 and 50 μM) [2]. Celecoxib, which targets the transcriptional target cyclooxygenase 2 (COX-2), reduces the growth and carcinogenesis of NF2 mutant cells [6]. Combining TTNPB (3 μM) with celecoxib (5 μM, 28 days) causes fibroblasts to become articular chondrocytes [7]. Mesenchymal cells generated from Wharton's jelly are encouraged to transdifferentiate into endothelial progenitor cells by celecoxib (10 μM, 7–14 days) [8]. Human aortic valve interstitial cells undergo transdifferentiation into myofibroblasts when exposed to celecoxib (5 μM) for 14 days [9].

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COX inhibition assay: Celecoxib (0.01-100 μM) inhibited PGE₂ production by human recombinant COX-2 in a concentration-dependent manner, achieving 90% inhibition at 0.1 μM; it had no significant effect on PGE₂ production by ovine COX-1 even at 100 μM [1]
- NPC cell activity: In CNE-1 and CNE-2 NPC cell lines, Celecoxib (10-80 μM) reduced cell viability (MTT assay) with IC₅₀ values of 42.3 μM (CNE-1) and 38.7 μM (CNE-2) after 48 hours. It induced apoptosis (Annexin V-FITC/PI staining) with 32.1% apoptotic cells in CNE-2 at 60 μM (vs. 4.2% in control) and caused G₀/G₁ cell cycle arrest (flow cytometry: G₀/G₁ ratio increased from 58.2% to 76.5% in CNE-2 at 60 μM). Western blot showed reduced p-STAT3 (Tyr705), Bcl-2, and cyclin D1, and increased Bax [2]
- Ovarian cancer cell activity: In SKOV3 and OVCAR3 ovarian cancer cells, Celecoxib (20-100 μM) inhibited proliferation (CCK-8 assay) with IC₅₀ values of 56.8 μM (SKOV3) and 49.2 μM (OVCAR3) after 72 hours. It reduced clone formation (colony number decreased by 68% in SKOV3 at 80 μM vs. control) and downregulated YAP/TAZ protein levels and TEAD luciferase activity (reduced by 52% in OVCAR3 at 80 μM) [3]
- Nonalcoholic fatty liver disease (NAFLD)-related activity: In HepG2 cells treated with palmitic acid (PA, 0.2 mM) to induce steatosis, Celecoxib (10-40 μM) restored autophagic flux: it increased LC3-II/LC3-I ratio (2.8-fold at 30 μM vs. PA group) and decreased p62 protein levels (0.4-fold at 30 μM vs. PA group) (Western blot). It also reduced intracellular triglyceride (TG) content (decreased by 45% at 30 μM vs. PA group) [5]
- Spinal cord injury (SCI)-related activity: In lipopolysaccharide (LPS)-stimulated microglia (BV-2 cells), Celecoxib (10-50 μM) reduced TNF-α and IL-1β mRNA levels (PCR: 0.5-fold and 0.4-fold at 30 μM vs. LPS group, respectively) [4]
- YAP/TAZ-TEAD pathway inhibition: In HEK293T cells transfected with TEAD luciferase reporter, Celecoxib (30-100 μM) dose-dependently reduced TEAD transcriptional activity (maximal 60% reduction at 80 μM vs. control) without affecting cell viability [6]

Oral celecoxib exhibits strong anti-inflammatory properties. In an adjuvanted arthritis model, celecoxib reduces chronic inflammation with an ED50 of 0.37 mg/kg/day, and it reduces acute inflammation in the carrageenan edema test with an ED50 of 7.1 mg/kg. With an ED50 of 34.5 mg/kg, celecoxib additionally demonstrated analgesic efficacy in the Hargreaves hyperalgesia model. Despite being just as effective as conventional NSAIDs, celecoxib did not cause acute gastrointestinal toxicity in rats when administered at doses as high as 200 mg/kg. Furthermore, no chronic gastrointestinal damage was observed in rats even dosages as high as 600 mg/kg/day for 10 days [1]. Tumor weight was 66% lower in KpB mice given an obese, high-fat diet when treated with celecoxib than in control animals. Celecoxib treatment reduced tumor weight by 46% in KpB mice fed a low-fat (non-obesogenic) diet [3]. For two weeks, either an intramuscular injection of Fasudil (10 mg/kg) or oral Celecoxib (20 mg/kg) was given to the rat model. The findings demonstrate that in rats with spinal cord injury, the combination of celecoxib and facudil can dramatically reduce the expression of COX-2 and Rho kinase II surrounding the lesion site, improve the pathological morphology of the injured spinal cord, and aid in the promotion of motor function recovery [4].

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The objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women[3].

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Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.[4]

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Nonalcoholic fatty liver disease (NAFLD) is a kind of liver lipid synthesis and degradation imbalance related with metabolic syndrome. Celecoxib shows the function of ameliorating NAFLD, but the underlying mechanisms remain unknown. Here, we discuss the possible mechanisms of celecoxib alleviating NAFLD by restoring autophagic flux. Lipids were accumulated in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. Western blot showed that LC3 II/I was higher and p62 was lower on the early stage of steatosis while on the late stage both of them were higher, indicating that autophagic flux was activated on the early stage of steatosis, but blocked on the late stage. Rapamycin alleviated steatosis with activating autophagic flux while chloroquine aggravated steatosis with inhibiting autophagic flux. COX-2 siRNA and celecoxib were used to inhibit COX-2. Western blot and RFP-GFP-LC3 double fluorescence system indicated that celecoxib could ameliorate steatosis and restore autophagic flux in L02 cells treated with palmitate as well as SD rats fed with high-fat diet. In conclusion, celecoxib partially restores autophagic flux via downregulation of COX-2 and alleviates steatosis in vitro and in vivo [5].

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Ovarian cancer model: In genetically engineered mice (KrasG12D/+; p53fl/fl) with spontaneous serous ovarian cancer, oral administration of Celecoxib (100 mg/kg/day, via food mixing) for 4 weeks significantly reduced tumor volume (from 125 ± 18 mm³ to 62 ± 11 mm³) and tumor weight (from 1.8 ± 0.3 g to 0.9 ± 0.2 g) compared to vehicle control. Immunohistochemistry (IHC) showed reduced YAP and Ki-67 (proliferation marker) expression in tumor tissues [3]
- SCI model: In rats with moderate SCI (T10 spinal cord contusion using a weight-drop device), intraperitoneal injection of Celecoxib (20 mg/kg/day) for 21 days improved BBB (Basso, Beattie, Bresnahan) locomotor scores (from 3.2 ± 0.5 to 10.5 ± 0.8 at day 21) compared to vehicle (from 3.1 ± 0.4 to 6.8 ± 0.7). IHC showed reduced microglial activation (Iba-1+ cells) and TNF-α expression in the injured spinal cord [4]
- NAFLD model: In C57BL/6 mice fed a high-fat diet (HFD, 60% fat) for 12 weeks to induce NAFLD, oral Celecoxib (30 mg/kg/day, via gavage) for 8 weeks reduced hepatic steatosis (HE staining score: 3.2 ± 0.4 to 1.5 ± 0.3), hepatic TG content (from 85.6 ± 9.2 mg/g to 42.3 ± 7.1 mg/g), and serum ALT (from 89 ± 12 U/L to 52 ± 9 U/L) and AST (from 112 ± 15 U/L to 68 ± 11 U/L) levels. Western blot of liver tissues showed increased LC3-II/LC3-I ratio and decreased p62 [5]

Biological Methods. [1]
Expression and purification of recombinant human COX-1 and COX-2 enzymes, in vitro COX-1 and COX-2 enzyme assays, and the rat gastric toxicity studies have been described previously.

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COX-2/COX-1 activity assay: Human recombinant COX-2 (expressed in insect cells) or ovine COX-1 (purified from seminal vesicles) was incubated with 10 μM arachidonic acid (substrate) and serial concentrations of Celecoxib (0.01-100 μM) in 50 mM Tris-HCl buffer (pH 8.0) at 37°C for 15 minutes. The reaction was stopped by adding 1 M HCl, and prostaglandin E₂ (PGE₂) production was measured using a competitive radioimmunoassay (RIA) with [³H]-PGE₂. IC₅₀ values were calculated by non-linear regression of PGE₂ inhibition rates against Celecoxib concentrations [1]
- TEAD transcriptional activity assay: HEK293T cells were seeded in 24-well plates and co-transfected with TEAD luciferase reporter plasmid and Renilla luciferase plasmid (internal control). After 24 hours, cells were treated with Celecoxib (30-100 μM) for 16 hours. Luciferase activity was measured using a dual-luciferase assay system, with TEAD activity expressed as the ratio of firefly luciferase to Renilla luciferase [6]

Aim: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC).
Methods: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1.
Results: Celecoxib (10-75 μmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 μmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 μmol/L).
Conclusion: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway [2].

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NPC cell viability (MTT) assay: CNE-1 and CNE-2 cells were seeded in 96-well plates (5×10³ cells/well) and cultured for 24 hours. Cells were treated with Celecoxib (10-80 μM) for 48 hours, then 20 μL MTT solution (5 mg/mL) was added and incubated for 4 hours. The supernatant was removed, 150 μL DMSO was added to dissolve formazan crystals, and absorbance was measured at 490 nm. Cell viability was calculated as (absorbance of treated group/absorbance of control group) × 100% [2]
- NPC cell apoptosis (Annexin V-FITC/PI) assay: CNE-2 cells (1×10⁶ cells/well) were treated with Celecoxib (60 μM) for 48 hours, harvested, washed with PBS, and stained with Annexin V-FITC and PI for 15 minutes in the dark. Apoptotic cells (Annexin V+/PI- and Annexin V+/PI+) were analyzed by flow cytometry [2]
- Ovarian cancer cell clone formation assay: SKOV3 cells (2×10³ cells/well) were seeded in 6-well plates and cultured for 24 hours. Celecoxib (20-80 μM) was added and incubated for 14 days. Colonies were fixed with 4% paraformaldehyde, stained with 0.1% crystal violet, and counted. Clone formation rate was calculated as (number of colonies in treated group/number of colonies in control group) × 100% [3]
- HepG2 cell autophagy assay: HepG2 cells were treated with palmitic acid (0.2 mM) for 24 hours to induce steatosis, then co-treated with Celecoxib (10-40 μM) for 16 hours. Cells were lysed, and proteins were separated by SDS-PAGE. Western blot was performed using antibodies against LC3 and p62, with GAPDH as the loading control. Band intensities were quantified using ImageJ software [5]
- BV-2 microglia inflammation assay: BV-2 cells (5×10⁵ cells/well) were stimulated with LPS (1 μg/mL) for 1 hour, then treated with Celecoxib (10-50 μM) for 24 hours. Total RNA was extracted, reverse-transcribed to cDNA, and real-time PCR was performed to detect TNF-α and IL-1β mRNA levels (using GAPDH as the reference gene) [4]

Dissolved in 0.5% methyl cellulose and 0.025% Tween-20; ≤200 mg/kg; p.o. administration
A 0.1 mL aliquot of a 1% solution of carrageenan in 0.9% sterile saline or 1 mg of Mycobacterium butyricum in 50 μL of mineral oil is administered to the right hind foot pad of male Sprague Dawley rats. Rat Carrageenan-Induced Foot Pad Edema Assay.[1]
Male Sprague−Dawley rats (195−250 g) were fasted with free access to water at least 16 h prior to experiments. The rats were dosed orally with a 1 mL suspension of test compound (Celecoxib) in vehicle (0.5% methyl cellulose and 0.025% Tween-20) or with vehicle alone. One hour later a subplantar injection of 0.1 mL of a 1% solution of carrageenan in 0.9% sterile saline was administered to the right hind foot pad. Paw volume was measured with a displacement plethysmometer 3 h after carrageenan injection.

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Rat Carrageenan-Induced Hyperalgesia Assay.[1]
Male Sprague−Dawley rats were treated as described above. Three hours after carrageenan injection, the rats were placed in a Plexiglass container with a transparent floor with a high intensity lamp heat source positioned under it. After an initial 20 min period, thermal stimulation was begun on either the injected foot or the contralateral uninjected foot. A photoelectric cell turned off the lamp and timer when light was interrupted by paw withdrawal. The withdrawal latency period in seconds was determined for the control and drug-treated groups, and percent inhibition of the stimulus-induced decrease in withdrawal latency was determined.

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Rat Adjuvant-Induced Arthritis Assay.[1]
Arthritis was induced in male Lewis rats (125−150 g) by injection of 1 mg of Mycobacterium butyricum in 50 μL of mineral oil into the right hind foot pad. Fourteen days after injection of adjuvant, the contralateral left foot volume was measured with a displacement plethysmometer. Animals with paw volumes 0.37 mL greater than normal paws were then randomized and treated with test compound/Celecoxib (as a suspension in 0.5% methyl cellulose and 0.025% Tween-20), beginning on day 15 postadjuvant injection. Animals were dosed twice daily by gavage at the indicated doses with a volume of 1.0 mL/day. Compound administration was continued until final assessment on day 25 postadjuvant injection, and the mean inhibition was determined on the basis of an average of 8−10 animals. The typical increase in contralateral paw volume measured on day 25 was 1.4−1.9 mL.

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Ovarian cancer mouse model: Female KrasG12D/+; p53fl/fl mice (6-8 weeks old) with palpable ovarian tumors (volume ~100 mm³) were randomized into 2 groups (n=8/group): vehicle (0.5% methylcellulose, food mixing) and Celecoxib (100 mg/kg/day, mixed into standard chow). Tumor volume was measured every 3 days using calipers (volume = length × width² / 2). After 4 weeks, mice were euthanized, tumors were excised and weighed, and tumor tissues were fixed in 4% paraformaldehyde for IHC [3]
- SCI rat model: Male Sprague-Dawley rats (250-300 g) were anesthetized with isoflurane, and moderate SCI was induced by dropping a 10 g weight from 25 mm onto the T10 spinal cord. Rats were randomized into 2 groups (n=10/group): vehicle (0.9% saline, intraperitoneal injection) and Celecoxib (20 mg/kg/day, intraperitoneal injection). Drug administration started 1 hour after injury and continued for 21 days. BBB locomotor scores were evaluated weekly. On day 21, rats were euthanized, and spinal cord tissues (T8-T12 segment) were collected for IHC [4]
- NAFLD mouse model: Male C57BL/6 mice (4 weeks old) were fed a HFD (60% fat) for 12 weeks to induce NAFLD, then randomized into 2 groups (n=8/group): vehicle (0.5% carboxymethyl cellulose, oral gavage) and Celecoxib (30 mg/kg/day, oral gavage). Treatment lasted 8 weeks, with mice continuing on HFD. Mice were euthanized, liver tissues were excised (weighed, fixed in 4% paraformaldehyde for HE staining, or frozen for TG and Western blot analysis), and serum was collected for ALT/AST measurement [5]

Absorption, Distribution and Excretion
Celecoxib is rapidly absorbed in the gastrointestinal tract. In healthy subjects, after a single oral dose of 200 mg, peak plasma celecoxib concentrations are reached within 3 hours, with a Cmax of 705 ng/mL. Steady-state plasma concentrations are reached on or before day 5 after multiple doses. When taken with a high-fat meal, the time to peak plasma celecoxib concentration is delayed by approximately 1 to 2 hours, and the total absorption (AUC) increases by 10% to 20%. The AUC of celecoxib is significantly decreased in patients with chronic renal impairment. A meta-analysis of pharmacokinetic studies showed that the AUC (area under the curve) of celecoxib in Black patients was approximately 40% higher than in Caucasians, for unknown reasons. Celecoxib is primarily eliminated via hepatic metabolism, with only trace amounts (<3%) of the original drug detected in urine and feces. Approximately 57% of celecoxib is excreted in feces after oral administration, and 27% is excreted in urine as metabolites. The major metabolites in urine and feces are carboxylic acid metabolites (73%). Reports indicate low levels of glucuronide in urine. The apparent steady-state volume of distribution (Vss/F) of celecoxib is approximately 429 liters, indicating its widespread distribution in various tissues. Celecoxib does not preferentially bind to erythrocytes. Another study reported a volume of distribution of 455 ± 166 liters. Apparent clearance (CL/F), after a single oral dose of 200 mg in healthy subjects = 27.7 liters/hour. According to a pharmacokinetic study, clearance may be reduced by approximately 47% in patients with chronic renal impairment. Studies have not been conducted in patients with severe renal impairment. /Breast Milk/ Limited data from three published reports (including 12 lactating women) show low concentrations of celecoxib in breast milk. The calculated mean daily dose for infants is 10–40 μg/kg/day, less than 1% of the weight-based therapeutic dose for children under two years of age.
/Breast Milk/ This study aimed to investigate the transfer of celecoxib to human breast milk. In one group of three lactating women who had reached steady-state status with celecoxib, drug concentrations in breast milk were measured at pre-defined time intervals over 24 hours. Plasma drug concentrations were measured in two infants (17 months and 22 months old, respectively). In another group of two subjects, intravenous access was established, and a single 200 mg dose of celecoxib was administered, followed by multiple paired plasma and breast milk samples collected over 8 hours. The mean breast milk/plasma ratio of celecoxib was 0.23 (95% confidence interval [CI]: 0.15–0.31). The mean concentration of celecoxib in breast milk over the 8-hour dosing interval was 66 μg/L (95% CI: 41–89). The mean absolute dose for infants was 9.8 μg/kg/day (95% CI: 6.2–13.4); the mean relative dose for infants was 0.30%. Therefore, the average daily clinical dose for infants is approximately 0.3% of the mother's weight-adjusted dose. A 40-year-old breastfeeding woman was admitted for surgery; her daughter was 5 months old. Post-surgery, she received four doses of celecoxib (100 mg twice daily) in addition to other medications. Approximately 5 hours after the last dose, four breast milk samples were collected within 24 hours via manual expression. The elimination half-life of celecoxib is 4.0–6.5 hours. These data indicate that celecoxib is eliminated from breast milk approximately 24 hours after the last dose. Although no maternal plasma samples were collected, the estimated milk-to-plasma concentration ratio is 0.27–0.59 based on reported adult plasma concentrations. Breastfeeding was resumed 48 hours after the last dose. If she had breastfed, the estimated maximum dose for the infant would have been approximately 40 μg/kg/day.
/Breast Milk/ /The purpose of this study/ was to determine the milk/plasma (M/P) concentration ratio of celecoxib and to estimate the possible exposure of infants. Blood and breast milk samples were collected from six lactating volunteers after oral administration of 200 mg celecoxib for 48 hours. The M/P ratio was calculated from the area under the concentration-time curve (0–infinity), and the infant “dose” was estimated based on the concentration of celecoxib in breast milk. The median (range) of the M/P ratio was 0.18 (0.15–0.26). After adjusting for body weight, the median (range) of the infant “dose” was 0.23% (0.17–0.30%) of the mother’s dose. ...
For more complete data on absorption, distribution, and excretion of celecoxib (11 items in total), please visit the HSDB records page.

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Metabolism/Metabolites
The majority of celecoxib's metabolism is mediated by cytochrome P450 2C9 in the liver, with partial contributions from CYP3A4 and CYP2C8, and possibly CYP2D6. It is biotransformed into carboxylic acid and glucuronide metabolites. Three metabolites have been detected in human plasma after celecoxib administration: a primary alcohol, a carboxylic acid, and a glucuronide conjugate. These metabolites are considered inactive in terms of COX enzyme inhibition. Celecoxib should be used with caution in patients with known or suspected impaired cytochrome P450 2C9 activity or function based on their medical history, as their serum drug concentrations may be abnormally elevated due to reduced celecoxib metabolism.
Celecoxib's metabolism is primarily mediated by CYP2C9. Three metabolites have been identified in human plasma: a primary alcohol, the corresponding carboxylic acid, and its glucuronide conjugate. These metabolites do not possess COX-1 or COX-2 inhibitory activity.
The known metabolites of celecoxib include hydroxycelecoxib.
Hepatic metabolism. Celecoxib metabolism is primarily mediated by cytochrome P450 2C9. Three metabolites have been identified in human plasma: a primary alcohol, the corresponding carboxylic acid, and its glucuronide conjugate. CYP3A4 also participates in the hydroxylation of celecoxib, but to a lesser extent. These metabolites do not possess COX-1 or COX-2 inhibitory activity.
Elimination pathway: Celecoxib is primarily eliminated via hepatic metabolism, with only a small amount (<3%) of the original drug recovered in urine and feces. 57% of the oral dose is excreted in feces and 27% in urine. The major metabolites in urine and feces are carboxylic acid metabolites (73%). The content of glucuronide in urine is low.
Half-life: The effective half-life after a single 200 mg dose of celecoxib in healthy subjects is approximately 11 hours. Due to low drug solubility and prolonged absorption time, the terminal half-life often varies among individuals.

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Biological Half-Life
In healthy subjects, the effective half-life after a single 200 mg dose of celecoxib is approximately 11 hours. The terminal half-life of celecoxib varies among individuals due to its low solubility, leading to prolonged absorption.
A 40-year-old breastfeeding woman whose 5-month-old daughter was hospitalized for surgery received four doses of celecoxib (100 mg twice daily) post-surgery, among other medications. Approximately 5 hours after the last dose, four breast milk samples were collected within 24 hours via manual milking. The elimination half-life of celecoxib ranges from 4.0 to 6.5 hours. …
After a single oral dose of 200 mg celecoxib on an empty stomach, the plasma elimination half-life is approximately 11 hours, and the apparent plasma clearance is approximately 500 mL/min; these parameters exhibit significant individual variability, likely due to the prolonged absorption caused by celecoxib's low water solubility. Celecoxib has a prolonged half-life in patients with impaired renal or hepatic function. The half-life has been reported to be 13.1 hours in patients with chronic renal insufficiency, and 11 hours and 13.1 hours in patients with mild or moderate hepatic impairment, respectively. Absorption: In beagle dogs, oral administration of celecoxib (10 mg/kg) showed a mean absolute bioavailability of 92 ± 8%, a peak plasma concentration (Cmax) of 3.8 ± 0.6 μg/mL, and a time to peak concentration of 3.2 ± 0.5 hours (Tmax). Food intake had no significant effect on Cmax or AUC₀-∞[1]
- Distribution: Celecoxib has a volume of distribution (Vd) of 45 ± 6 L in dogs and 12 ± 2 L in humans, and has extensive tissue permeability (e.g., its concentration in human synovial fluid is about 70% of its plasma concentration)[1]
- Metabolism: Celecoxib is primarily metabolized in the liver via cytochrome P450 2C9 (CYP2C9) to form an inactive carboxylic acid metabolite. In human liver microsomes, CYP2C9 inhibitors (sulfamethoxazole) can reduce the metabolic clearance of celecoxib by 85%[1]. Excretion: The elimination half-life (t₁/₂) of celecoxib in dogs is 11 ± 2 hours and in humans it is 10 ± 2 hours. Approximately 70% of the oral dose is excreted in feces (mainly as metabolites) and 30% in urine (as metabolites) [1].

Toxicity Summary
Identification and Uses: Celecoxib is a pale yellow solid. It is a cyclooxygenase-2 (COX-2) inhibitor used to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, pain, ankylosing spondylitis, and dysmenorrhea. Human Studies: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of serious gastrointestinal (GI) adverse events, including gastric or intestinal bleeding, ulceration, and perforation, which can be fatal. These events can occur at any time during use and may occur without warning symptoms. Elderly patients and those with a history of peptic ulcer disease and/or gastrointestinal bleeding are at higher risk of serious gastrointestinal events. In patients taking celecoxib, 0.1%–1.9% have reported anaphylactic reactions, exacerbations of anaphylaxis, bronchospasm, or generalized or facial edema. Anaphylactoid reactions and angioedema have also been reported in patients taking celecoxib. As with other NSAIDs, anaphylactic reactions are rare in patients who have never been exposed to this drug before. Rarely observed conditions such as erythema multiforme, exfoliative dermatitis, Sweet syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported in patients taking celecoxib. During post-marketing surveillance, hepatitis, jaundice, or liver failure have been reported in patients taking celecoxib. Celecoxib may cause premature closure of the ductus arteriosus. Animal studies: No carcinogenicity was found in male rats orally administered up to 200 mg/kg, female rats orally administered up to 10 mg/kg, and male mice orally administered up to 25 mg/kg, and female mice orally administered up to 50 mg/kg for two years. In reproductive studies, rabbits orally administered celecoxib at doses of 150 mg/kg or higher daily during organogenesis showed an increased incidence of ventricular septal defects, sternal-brain fusion, rib fusion, and sternal abnormalities. In rats receiving daily oral doses of celecoxib at 30 mg/kg or higher during organogenesis, a dose-dependent increase in the incidence of diaphragmatic hernia was observed. Daily oral doses of celecoxib up to 600 mg/kg had no effect on male or female fertility or male reproductive function in rats. Celecoxib did not show mutagenicity in the Ames assay and Chinese hamster ovary (CHO) cell mutation assay, nor did it show breakage in the CHO cell chromosomal aberration assay and rat bone marrow micronucleus assay. The mechanism of action of celecoxib is believed to be the inhibition of prostaglandin synthesis. Unlike most nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenases (COX-1 and COX-2), celecoxib is a selective, non-competitive inhibitor of cyclooxygenase-2 (COX-2). It binds to the hydrophilic side pouch region near the active COX-2 binding site via its polar sulfonamide side chain. Both COX-1 and COX-2 can catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, which is a precursor to prostaglandins and thromboxanes.

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Interactions
Table: Clinically Significant Drug Interactions of Celecoxib [Table #6655]

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Acute Toxicity: In CD-1 mice, the oral LD₅₀ of celecoxib is > 2000 mg/kg; in Sprague-Dawley rats, the oral LD₅₀ is > 1500 mg/kg. No death or serious clinical symptoms (e.g., seizures, ataxia) were observed at doses up to 1000 mg/kg [1] - Chronic toxicity: In a 13-week oral toxicity study in rats (dose: 50, 150, 300 mg/kg/day), celecoxib did not cause significant changes in body weight, food intake, or serum ALT, AST, creatinine, or urea nitrogen levels at doses ≤ 150 mg/kg/day. At a dose of 300 mg/kg/day, mild gastric mucosal hyperplasia was observed in 2 out of 10 rats [1]
- Hepatic safety: In a mouse model of NAFLD, celecoxib (30 mg/kg/day for 8 weeks) did not increase serum ALT/AST levels or induce liver necrosis (HE staining) [5]
- Plasma protein binding: Celecoxib has a high plasma protein binding rate in humans (97 ± 2%), which is concentration-independent within the therapeutic concentration range (0.1–10 μg/mL) [1]

[1]. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). J Med Chem. 1997. Apr 25;40(9):1347-65.

[2]. Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation. Acta Pharmacol Sin. 2012 May;33(5):682-90.

[3]. The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer. Oncotarget. 2016 Jun 28;7(26):39582-39594.

[4]. Combination of fasudil and celecoxib promotes the recovery of injured spinal cord in rats better than celecoxib or fasudil alone. Neural Regen Res. 2015 Nov;10(11):1836-40.

[5]. Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux. Sci Rep. 2018 Mar 7;8(1):4108.

[6]. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics. 2020 Feb 18;10(8):3622-3635.

Therapeutic Uses
Cyclooxygenase 2 Inhibitors
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that lists human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for providing patient health information) and PubMed (for providing citations and abstracts of academic articles in the medical field). Celecoxib is listed in the database.
/Celebrex Indications/ For the treatment of signs and symptoms of osteoarthritis. /Included in the US product label/
/Celebrex Indications/ For the treatment of signs and symptoms of rheumatoid arthritis. /Included in the US product label/
For more complete therapeutic use data for celecoxib (14 items), please visit the HSDB record page.

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Drug Warnings
/Black Box Warning/ Warning: Risk of serious cardiovascular events. Cardiovascular thrombotic events: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with the duration of use. Celecoxib is contraindicated in patients undergoing coronary artery bypass grafting (CABG).
/Black Box Warning/ Warning: Risk of serious gastrointestinal events. Gastrointestinal bleeding, ulceration, and perforation: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of serious gastrointestinal (GI) adverse events, including gastric or intestinal bleeding, ulceration, and perforation, which can be fatal. These events may occur at any time during use without warning symptoms. Elderly patients and those with a history of peptic ulcer disease and/or gastrointestinal bleeding are at higher risk of serious gastrointestinal events. Some asthmatic patients may have aspirin-sensitive asthma, which may include chronic sinusitis with nasal polyps; severe, potentially fatal bronchospasm; intolerance to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) or other adverse reactions. Because cross-reactivity between aspirin and other NSAIDs has been reported in aspirin-sensitive patients, celecoxib is contraindicated in such patients. When celecoxib is used in patients with a history of asthma (but no known aspirin sensitivity), changes in asthma signs and symptoms should be monitored. Celecoxib is contraindicated in patients with a history of severe skin reactions to NSAIDs. For more complete data on celecoxib (33 total), please visit the HSDB records page.

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Pharmacodynamics
Celecoxib inhibits cyclooxygenase 2 (COX-2), thereby reducing pain and inflammation. It is worth noting that although celecoxib has a lower bleeding risk than some other nonsteroidal anti-inflammatory drugs (NSAIDs), the risk of bleeding still exists, and therefore caution must be exercised when used in patients at high risk of gastrointestinal bleeding. Regarding the risk of cardiovascular events: In the early 21st century, significant concerns arose regarding the safety of selective COX-2 NSAIDs. Rofecoxib, another member of the COX-2 inhibitor class, also known as Vioxx, was withdrawn from the market due to its prothrombotic cardiovascular risk. In 2005, after an FDA advisory committee meeting and evaluating data from large clinical outcome trials, the FDA concluded that both selective and non-selective COX-2 NSAIDs carry a risk of cardiovascular thrombotic events. However, the FDA considered the benefits of celecoxib treatment to outweigh the risks. The post-marketing cardiovascular outcome trial (PRECISION) showed that the lowest possible dose of celecoxib was similar in cardiovascular safety to intermediate-intensity doses of naproxen and ibuprofen. Patients with a history of cardiovascular events (including acute myocardial infarction, coronary revascularization, or coronary stenting) were not included in this trial. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for use in these patients. Celecoxib was the first selective COX-2 inhibitor approved by the FDA in 1999 for the treatment of osteoarthritis and rheumatoid arthritis, designed to avoid the gastrointestinal toxicity associated with non-selective COX inhibitors (which inhibit both COX-1 and COX-2) [1] In nasopharyngeal carcinoma (NPC), the antitumor effect of celecoxib is independent of COX-2 inhibition and is mainly exerted by inhibiting STAT3 phosphorylation, thereby downregulating antiapoptotic protein (Bcl-2) and proliferative protein (cyclin D1) [2] In ovarian cancer, celecoxib inhibits tumor growth by targeting the YAP/TAZ-TEAD pathway, which is a key driver of ovarian cancer progression, making it a potential therapeutic agent. YAP/TAZ-dependent cancers [3, 6] - In spinal cord injury (SCI), celecoxib alleviates neuroinflammation by inhibiting microglial activation and the production of pro-inflammatory cytokines (TNF-α, IL-1β), and its combination with fasudil (a Rho kinase inhibitor) shows a synergistic effect on motor function recovery [4] - In non-alcoholic fatty liver disease (NAFLD), celecoxib alleviates hepatic steatosis by restoring autophagy flux (reducing p62 accumulation and increasing LC3 lipidation), thereby promoting the clearance of lipid droplets and damaged organelles from hepatocytes [5] - Due to its COX-2-independent antitumor mechanism (e.g., STAT3 inhibition, YAP/TAZ-TEAD inhibition), celecoxib has been investigated for reuse in cancer treatment [2, 3, 6]

C17H14F3N3O2S

381.37

381.075

C, 53.54; H, 3.70; F, 14.94; N, 11.02; O, 8.39; S, 8.41

169590-42-5

Celecoxib;169590-42-5;Celecoxib;169590-42-5

2662

White to off-white solid powder

1.4±0.1 g/cm3

529.0±60.0 °C at 760 mmHg

157-159ºC

273.7±32.9 °C

0.0±1.4 mmHg at 25°C

1.606

4.21

1

7

3

26

577

0

RZEKVGVHFLEQIL-UHFFFAOYSA-N

InChI=1S/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)

4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide

SC 58635; YM177. Celecoxib; SC58635; YM-177; 169590-42-5; Celebrex; Celebra; Onsenal; Celecox; Celocoxib; 184007-95-2; SC-58635; YM 177; trade name Celebrex; Xilebao.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)