CAS 169590-42-5|celecoxib|4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide|4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide|4-[5-(4-Methylphenyl)-...

General Information

Structure

Molecular Formula

C₁₇H₁₄F₃N₃O₂S

Molecular Mass

381.3721696

Exact Mass

381.07588236

Charge

InChI

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)

InChIKey

RZEKVGVHFLEQIL-UHFFFAOYSA-N

Canonic Smiles

Cc1ccc(cc1)c1cc(nn1c1ccc(cc1)S(=O)(=O)N)C(F)(F)F

Isomeric Smiles

S(=O)(=O)(N)c1ccc(n2nc(cc2c2ccc(cc2)C)C(F)(F)F)cc1

Calculated Properties

JChem

Acid pKa

10.70145

H Acceptors

H Donor

LogD (pH = 5.5)

4.009439

LogD (pH = 7.4)

4.0092497

Log P

4.009442

Molar Refractivity

92.2342

Polarizability

36.37739

Polar Surface Area

77.98

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

3.99

LOG S

-4.88

Solubility (Water)

5.03e-03 g/l

Data Source

Names and Identifiers

IUPAC Traditional name

celecoxib 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide

Synonyms

4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-pyrazol-1-yl]benzenesulfonamideCelebrexCelebra CelecoxibCelocoxibcelecoxibPHA-00846533YM-177SC-58635CP-598107CJ-0163774-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamideCelecoxibPF-003455494-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamideSC 586354-[5-(4-Methylphenyl)-3-trifluoromethyl)-1H-pyrazol-yl]benzenesulfonamideCelecoxYM 177

IUPAC name

4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzene-1-sulfonamide

Brand Name

CelebraCelebrex

Names and Identifiers

Registration numbers

CAS Number

MDL Number

ATC CODE

CHEBI ID

KEGG ID

Unique Ingredient Identifier

Wikipedia Title

CHEMBL

Medline Plus

Chemspider ID

DrugBank ID

PubChem CID

PubChem SID

Registration numbers

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

DrugBank

DB00482

Drug Groups

approved; investigational

Description

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.

Indication

For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis

Pharmacology

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Celecoxib is used to treat rheumatoid arthritis, osteoarthritis, and familial adenomatous polyposis (FAP). Because of its lack of platelet effects, celecoxib is not a substitute for aspirin for cardiovascular prophylaxis. It is not known if there are any effects of celecoxib on platelets that may contribute to the increased risk of serious cardiovascular thrombotic adverse events associated with the use of celecoxib. Inhibition of PGE2 synthesis may lead to sodium and water retention through increased reabsorption in the renal medullary thick ascending loop of Henle and perhaps other segments of the distal nephron. In the collecting ducts, PGE2 appears to inhibit water reabsorption by counteracting the action of antidiuretic hormone.

Toxicity

Symptoms of overdose include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic. Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.

Absorption

Well absorbed in the gastrointestinal tract. When taken with a high fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%.

Half Life

Approximately 11 hours.

Protein Binding

97%, primarily to albumin and, to a lesser extent, a₁-acid glycoprotein.

Elimination

Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces.

Distribution

* 400 L

Clearance

* 500 mL/min

References

• Malhotra S, Shafiq N, Pandhi P: COX-2 inhibitors: a CLASS act or Just VIGORously promoted. MedGenMed. 2004 Mar 23;6(1):6. [Pubmed]

• Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS: Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000 Sep 13;284(10):1247-55. [Pubmed]

• Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 2005 Mar 17;352(11):1071-80. Epub 2005 Feb 15. [Pubmed]

• Yelland MJ, Nikles CJ, McNairn N, Del Mar CB, Schluter PJ, Brown RM: Celecoxib compared with sustained-release paracetamol for osteoarthritis: a series of n-of-1 trials. Rheumatology (Oxford). 2007 Jan;46(1):135-40. Epub 2006 Jun 15. [Pubmed]

• Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET: Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1261

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.

Features

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

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.

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.

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

[1] Penning TD, et al. J Med Chem, 1997, 40(9), 1347-1365.

[2] Liu DB, et al. Acta Pharmacol Sin, 2012, 33(5), 682-690.

[3] Hunter NR, et al. Int J Radiat Oncol Biol Phys, 2012, doi:10.1016/j.ijrobp.2012.04.025.

[4] Lampiasi N, et al. Cancer Lett, 2012, 322(1), 35-44.

[5] Li W, et al. Int J Mol Sci, 2011, 12(1), 668-681.

Wikipedia

Celecoxib

Sigma Aldrich

PZ0008

Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
Celecoxib is a non-steroidal, anti-inflammatory drug (NSAID) and a cyclooxygenase-2 (COX-2) selective inhibitor. Celecoxib is at least 10-20 times more selective for COX-2 over COX-1.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. PZ0008.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

TRC

C251000

A selective cyclooxygenase-2 (COX-2) inhibitor. Anti-inflammatory. Used in treatment of familial adenomatous polyposis.

Molecule Details

References

PubChem Literature

From Data Sources

• Malhotra S, Shafiq N, Pandhi P: COX-2 inhibitors: a CLASS act or Just VIGORously promoted. MedGenMed. 2004 Mar 23;6(1):6. Pubmed

• Li W, et al. Int J Mol Sci, 2011, 12(1), 668-681.

• Liu DB, et al. Acta Pharmacol Sin, 2012, 33(5), 682-690.

• Lampiasi N, et al. Cancer Lett, 2012, 322(1), 35-44.

• Hunter NR, et al. Int J Radiat Oncol Biol Phys, 2012, doi:10.1016/j.ijrobp.2012.04.025.

• Penning TD, et al. J Med Chem, 1997, 40(9), 1347-1365.

• Steinbach, G., et al.: N. Engl. J. Med., 342, 1946 (1998)

• Simon, L.S., et al.: Arthritis Rheum., 41, 1591 (1998)

• Silverstein, F.E., et al.: J. Am. Med. Assoc., 284, 1247 (1998)

• Lipsky, P.E. et al., J. Rheumatol., Suppl. 49, 1997, 24, 9-14; 20-24, (use)

• Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 25

• Hubbard, R.C. et al., J. Invest. Med., 1996, 44, 293A, (pharmacol)

• De Vleeschauwer, M. et al., Synlett, 1997, 375-377, (synth)

• Reddy, B.S. et al., Cancer Res., 1996, 56, 4566-4569; 1998, 58, 409-412, (pharmacol)

• Graul, A. et al., Drugs of the Future, 1997, 22, 711-714, (rev)

• Zhang, Y. et al., J. Pharmacol. Exp. Ther., 1997, 283, 1069-1075, (pharmacol)

• Pat. Coop. Treaty (WIPO), 1995, Searle, 95 15316; CA, 123, 340112h, (synth, pharmacol)

• Penning, T.D. et al., J. Med. Chem., 1997, 40, 1347-1365, (synth, pharmacol, pmr)

• Clemett, D. et al., Drugs, 2000, 59, 957-980, (rev)

• Kawamori, T. et al., Cancer Res., 1998, 58, 409-412, (pharmacol)

References

Bioactivity

PubChem BioAssay

Bioactivity