Celecoxib

• Catalog No.: S1261
• CAS Number: 169590-42-5
• M. F.: C17H14F3N3O2S
• M. W.: 381.3721696
• Storage: -20°C

SYNONYMS

• IUPAC name: 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide
• IUPAC Traditional name: celecoxib
• Synonyms: Celebra; Celebrex

DATABASE IDS

• CAS Number: 169590-42-5

PROPERTIES

• Target: COX
• Salt Data: Free Base
• Solubility: DMSO
• Storage Condition: -20°C

DETAILS

Description (English)

Research Area

• Description: Prostate cancer

Biological Activity

• Description: Celecoxib is a selective COX-2 inhibitor with IC50 of 40 nM.
• Targets: COX-2
• IC50: 40 nM ^[1]
• In Vitro: Celecoxib shows low sensitivity against COX-1 with IC50 of 15 μM. ^[1] Celecoxib shows an anti-proliferative effect on nasopharyngeal carcinoma (NPC) cell lines including HNE1 and CNE1-LMP1 with IC50 of 32.86 μM and 61.31 μM, respectively. ^[2]
• In Vivo: Celecoxib exhibits a potent, oral anti-inflammatory activity. Celecoxib reduces acute inflammation in the carrageenan edema assay and chronic inflammation in the adjuvant arthritis model with ED50 of 7.1 mg/kg and 0.37 mg/kg/day, respectively. In addition, Celecoxib also exhibits analgesic activity in the Hargreaves hyperalgesia model with ED50 of 34.5 mg/kg. Besides, Celecoxib produces no acute GI toxicity in rats at doses up to 200 mg/kg and no chronic GI toxicity in rats at doses up to 600 mg/kg/day over 10 days. ^[1] In a C3Hf/KamLaw female mouse model, Celecoxib increases median survival time of 105 days (range, 79-145 days) after 13.5 Gy local thoracic irradiation (LTI) alone to 142 days (range, 94-155 days). ^[3]
• Clinical Trials: Celecoxib is currently in Phase II clinical trials in patients with recurrent respiratory papillomatosis.

Combination Therapy

• Description: Combination treatment of Celecoxib and dehydroxymethyl-epoxyquinomicin (DHMEQ), an inhibitor of NF-κB produces the synergistic inhibitory effects on cell growth, NF-κB p65 DNA-binding capacity, and cell proliferation in HA22T/VGH and Huh-6 cell lines. ^[4] Combination of SC-560 and Celecoxib shows better antitumor activity with about 35.54% inhibition of tumor growth on human ovarian SKOV-3 carcinoma cells xenograft-bearing mice, while SC-560 and Celecoxib alone only results in inhibition of tumor growth by 13.57% and 15.16%, respectively. ^[5] Combination therapy of Celecoxib and cyclophosphamide is currently in Phase II clinical trials in patients with recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer.

Protocol

• Protocol: Kinase Assay ^[1]
• COX enzyme assay in vitro: Expression of COX protein in insect cells is determined by assessing PG-synthetic capability in homogenates from cells incubated for 3 days with COX-1 or COX-2 baculovirus. Cells expressing COX-1 or COX-2 are homogenized and incubated with arachidonic acid (10 μM). COX activity is determined by monitoring PG production. No COX activity is detected in mock-infected Sf9 cells. Celecoxib are preincubated with crude 1% CHAPS homogenates (2-10 μg of protein) for 10 minutes before addition of arachidonic acid. PGE2 formed is detected by ELISA after 10 minute incubation.
• Protocol: Cell Assay ^[2]
• Cell Lines: HNE1 and CNE1-LMP1
• Concentrations: 0-75 μM
• Incubation Time: 48 hours
• Methods: The antiproliferative effect of Celecoxib on NPC cells is assessed using an MTT assay. Cells are seeded into 96-well plates and allowed to attach for 24 hours. The cells are then treated with increasing concentrations of Celecoxib (0 to 75 μM) dissolved in DMSO (final concentration ≤0.1%) and incubated for up to 48 hours. After the incubation, 20 μL of MTT dye (5 mg/mL) are added to each well and cells are incubated at 37 °C for 4 hours. After removing the supernatants, the crystals are dissolved in DMSO and the absorbance is measured at 490 nm. The half-maximal inhibitory concentration (IC50) values and the 95% confidence intervals are calculated using probit regression using SPSS 15.0 software. The experiment is performed in triplicate and repeated at least three times.
• Protocol: Animal Study ^[1]
• Animal Models: 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.
• Formulation: Celecoxib is dissolved in 0.5% methyl cellulose and 0.025% Tween-20.
• Doses: ≤200 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Penning TD, et al. J Med Chem, 1997, 40(9), 1347-1365.
• References: [2] Liu DB, et al. Acta Pharmacol Sin, 2012, 33(5), 682-690.
• References: [3] Hunter NR, et al. Int J Radiat Oncol Biol Phys, 2012, doi:10.1016/j.ijrobp.2012.04.025.
• References: [4] Lampiasi N, et al. Cancer Lett, 2012, 322(1), 35-44.
• References: [5] Li W, et al. Int J Mol Sci, 2011, 12(1), 668-681.

REFERENCES

• Penning TD, et al. J Med Chem, 1997, 40(9), 1347-1365.
• Liu DB, et al. Acta Pharmacol Sin, 2012, 33(5), 682-690.
• Hunter NR, et al. Int J Radiat Oncol Biol Phys, 2012, doi:10.1016/j.ijrobp.2012.04.025.
• Lampiasi N, et al. Cancer Lett, 2012, 322(1), 35-44.
• Li W, et al. Int J Mol Sci, 2011, 12(1), 668-681.