Celecoxib
(right click,save link as to download,it is a temp file,please download as soon as possible, you can also use CTRL+S to save the whole html page)
Basic Info
| Common Name | Celecoxib(F05505) |
| 2D Structure | |
| 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. |
| FRCD ID | F05505 |
| CAS Number | 169590-42-5 |
| PubChem CID | 2662 |
| Formula | C17H14F3N3O2S |
| IUPAC Name | 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide |
| InChI Key | RZEKVGVHFLEQIL-UHFFFAOYSA-N |
| 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) |
| Canonical SMILES | CC1=CC=C(C=C1)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F |
| Isomeric SMILES | CC1=CC=C(C=C1)C2=CC(=NN2C3=CC=C(C=C3)S(=O)(=O)N)C(F)(F)F |
| Wikipedia | Celecoxib |
| Synonyms |
SC 58635
celecoxib
Celebrex
169590-42-5
Celebra
Onsenal
Celocoxib
Celecox
Xilebao
YM177
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Azoles |
| Subclass | Pyrazoles |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Phenylpyrazoles |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| Substituents | Phenylpyrazole - Benzenesulfonamide - Benzenesulfonyl group - Toluene - Monocyclic benzene moiety - Organosulfonic acid amide - Benzenoid - Organic sulfonic acid or derivatives - Organosulfonic acid or derivatives - Sulfonyl - Aminosulfonyl compound - Heteroaromatic compound - Azacycle - Organic oxide - Alkyl halide - Alkyl fluoride - Organopnictogen compound - Organosulfur compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Hydrocarbon derivative - Organic nitrogen compound - Organic oxygen compound - Aromatic heteromonocyclic compound |
| Description | This compound belongs to the class of organic compounds known as phenylpyrazoles. These are compounds containing a phenylpyrazole skeleton, which consists of a pyrazole bound to a phenyl group. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 381.373 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Complexity | 577 |
| Monoisotopic Mass | 381.076 |
| Exact Mass | 381.076 |
| XLogP | 3.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 26 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9713 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8866 |
| P-glycoprotein Substrate | Non-substrate | 0.9287 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8619 |
| Non-inhibitor | 0.7920 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8582 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4738 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.6237 |
| CYP450 2D6 Substrate | Substrate | 0.8919 |
| CYP450 3A4 Substrate | Non-substrate | 0.5751 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.7805 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.6172 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8594 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.7169 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.7959 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.7392 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9856 |
| Non-inhibitor | 0.8419 | |
| AMES Toxicity | Non AMES toxic | 0.7185 |
| Carcinogens | Non-carcinogens | 0.7905 |
| Fish Toxicity | High FHMT | 0.9891 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.7897 |
| Honey Bee Toxicity | Low HBT | 0.8783 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | III | 0.6499 |
| Carcinogenicity (Three-class) | Non-required | 0.7022 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.1816 | LogS |
| Caco-2 Permeability | 1.0149 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.3719 | LD50, mol/kg |
| Fish Toxicity | 1.5816 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.5421 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| COX-2/EP2-EP4/β-catenin signaling regulates patulin-induced intestinal cell proliferation and inflammation. | Toxicol Appl Pharmacol | 2018 Oct 1 | 30138657 |
| Pharmacokinetic drug interactions of the selective androgen receptor modulatorGTx-024(Enobosarm) with itraconazole, rifampin, probenecid, celecoxib androsuvastatin. | Invest New Drugs | 2016 Aug | 27105861 |
| Celecoxib, a COX-2 inhibitor, synergistically potentiates the anti-inflammatory activity of docosahexaenoic acid in macrophage cell line. | Immunopharmacol Immunotoxicol | 2016 | 26954392 |
| Interferon-alpha treatment induces depression-like behaviour accompanied byelevated hippocampal quinolinic acid levels in rats. | Behav Brain Res | 2015 Oct 15 | 26205824 |
| Evaluation of anti-osteoarthritic activity of Vigna mungo in papain induced osteoarthritis model. | Indian J Pharmacol | 2015 Jan-Feb | 25821313 |
| Determining cyclooxygenase-2 activity in three different test systems utilizing online-solid phase extraction-liquid chromatography-mass spectrometry for parallel quantification of prostaglandin E(2), D(2) and thromboxane B(2). | J Chromatogr A | 2015 Apr 24 | 25777050 |
| Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity. | PLoS One | 2015 | 26440517 |
| Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κBand COX-2 signaling. | PLoS One | 2014 Oct 21 | 25333664 |
| Antidepressant-like effect of celecoxib piroxicam in rat models of depression. | J Neural Transm (Vienna) | 2014 Jun | 24463888 |
| Development and characterization of a novel drug nanocarrier for oral delivery,based on self-assembled β-casein micelles. | J Control Release | 2012 Jun 10 | 22266050 |
| Determination of non-steroidal anti-inflammatory drugs and their metabolites inmilk by liquid chromatography-tandem mass spectrometry. | Anal Bioanal Chem | 2012 Jul | 22395450 |
| COX-2 inhibition does not reverse the increased sympathetic modulation in MSGobese rats. | Auton Neurosci | 2011 Dec 7 | 21824825 |
| Biomarkers of inflammation in cattle determining the effectiveness ofanti-inflammatory drugs. | J Vet Pharmacol Ther | 2010 Feb | 20444018 |
| Importance of cyclooxygenase 2-mediated low-grade inflammation in the developmentof fructose-induced insulin resistance in rats. | Chin J Physiol | 2009 Apr 30 | 19764341 |
| Colorectal cancer prevention: is an ounce of prevention worth a pound of cure? | Semin Oncol | 2005 Feb | 15726503 |
| Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors. | Drug Saf | 2005 | 16180941 |
| Distinct roles for cyclooxygenases 1 and 2 in interleukin-1-induced behavioral changes. | J Pharmacol Exp Ther | 2002 Sep | 12183660 |
| Warfarin and celecoxib interaction. | Ann Pharmacother | 2000 Mar | 10917378 |
Targets
- General Function:
- Prostaglandin-endoperoxide synthase activity
- Specific Function:
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
- Gene Name:
- PTGS2
- Uniprot ID:
- P35354
- Molecular Weight:
- 68995.625 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular Weight:
- 49761.245 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
- Gene Name:
- CYP2C9
- Uniprot ID:
- P11712
- Molecular Weight:
- 55627.365 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
- Gene Name:
- VDR
- Uniprot ID:
- P11473
- Molecular Weight:
- 48288.64 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Protein serine/threonine kinase activity
- Specific Function:
- Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.
- Gene Name:
- PDPK1
- Uniprot ID:
- O15530
- Molecular Weight:
- 63151.305 Da
References
- Kulp SK, Yang YT, Hung CC, Chen KF, Lai JP, Tseng PH, Fowble JW, Ward PJ, Chen CS: 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. Cancer Res. 2004 Feb 15;64(4):1444-51. [14973075 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]