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Drug-Target Interaction

Drug

show drug details
PubChem ID:2662
Structure:
Synonyms:
169590-42-5
184007-95-2
194044-54-7
1oq5
4-(5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonami
4-(5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
4-[5-(4-METHYLPHENYL)-3-(TRIFLUOROMETHYL)-1H-PYRAZOL-1-YL]BENZENESULFONAMIDE
4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1Hpyrazol-1-yl] benzenesulfonamide
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
AI-525
Benzenesulfonamide, 4-(5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-
Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
Benzenesulfonamide,4-(5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)
BSPBio_003596
C07589
C105934
C17H14F3N3O2S
CCRIS 8679
CEL
Celebra
Celebrex
Celebrex (TN)
Celecox
Celecoxib
Celecoxib (JAN/USAN/INN)
Celecoxib (SC-58635)
Celecoxib [USAN]
Celocoxib
CHEBI:41423
cMAP_000027
D00567
DB00482
DivK1c_000893
Heumann brand of celecoxib
HSDB 7038
I01-1033
IDI1_000893
KBio1_000893
KBio2_000912
KBio2_002351
KBio2_003480
KBio2_004919
KBio2_006048
KBio2_007487
KBio3_002830
KBio3_003037
KBioGR_000723
KBioGR_002351
KBioSS_000912
KBioSS_002354
KS-1041
LS-31667
Mack brand of celecoxib
MLS001165684
MLS001195656
MLS001304708
NCGC00091455-01
NCGC00091455-02
NCGC00091455-03
NCGC00091455-04
NCI60_041049
NINDS_000893
NSC719627
Onsenal
p-(5-p-Tolyl-3-(trifluoromethyl)pyrazol-1-yl)benzenesulfonamide
Parke Davis brand of celecoxib
Pfizer brand of celecoxib
Pharmacia brand of celecoxib
Pharmacia Spain brand of celecoxib
SC 58635
SC-58553, SC-58635
SC-58635
SC58635
Searle brand of celecoxib
SMR000550473
Solexa
SPBio_001512
SPECTRUM1503678
Spectrum2_001576
Spectrum3_001996
Spectrum4_000182
Spectrum5_001324
Spectrum_000432
STOCK6S-51468
TL8001323
TPI-336
UNM-0000305813
Xilebao
YM 177
YM-177
YM177
ZINC02570895
ATC-Codes:
Side-Effects:
Side-EffectFrequency
headache0.1465
hypertension0.125
dyspepsia0.0776
upper respiratory tract infection0.0754
diarrhea0.058166668
sinusitis0.0472
gastroesophageal reflux disease0.047
nausea0.036857147
abdominal pain0.035800003
back pain0.031200001
dyspnea0.028
insomnia0.023
rash0.021599999
pharyngitis0.0182
rhinitis0.017199999
flatulence0.017199999
peripheral edema0.016999999
vomiting0.0165
dizziness0.015833333
vasculitis0.0010
fever0.0010
pulmonary embolism0.0010
vascular disorders0.0010
gangrene0.0010
osteitis0.0010
myositis0.0010
interstitial nephritis0.0010
pancytopenia0.0010
ventricular fibrillation0.0010
ulceration0.0010
esophageal perforation0.0010
pain0.0010
pancreatitis0.0010
erythema multiforme0.0010
epilepsy0.0010
toxic epidermal necrolysis0.0010
gastrointestinal bleeding0.0010
myocardial infarction0.0010
cardiac disorders0.0010
hypoglycemia0.0010
thrombocytopenia0.0010
hyponatremia0.0010
intestinal perforation0.0010
jaundice0.0010
syncope0.0010
stevens johnson syndrome0.0010
acute renal failure0.0010
leukopenia0.0010
thrombophlebitis0.0010
heart failure0.0010
congestive heart failure0.0010
bleeding0.0010
hepatitis0.0010
menstrual disorder0.0010
skin erythema0.0010
mediastinal disorders0.0010
allergic reactions0.0010
cerebrovascular accident0.0010
bronchospasm0.0010
angioedema0.0010
anosmia0.0010
confusion0.0010
acute pancreatitis0.0010
connective tissue disorders0.0010
aseptic meningitis0.0010
colitis0.0010
cholelithiasis0.0010
arthritis0.0010
breast disorders0.0010
transient ischemic attacks0.0010
ataxia0.0010
sepsis0.0010
deep venous thrombosis0.0010
angina0.0010
aplastic anemia0.0010
hallucinations0.0010
exfoliative dermatitis0.0010
anaphylactic shock0.0010
agranulocytosis0.0010
dysmenorrhea0.0010
liver failure0.0010
intracranial hemorrhage0.0010
decreased hearing0.0010
increased sweating0
tinnitus0
neuropathy0
synovitis0
blurred vision0
photosensitivity0
pruritus0
hypophosphatemia0
thrombocythemia0
proteinuria0
pneumonia0
paresthesia0
urinary frequency0
skin nodule0
elevated blood pressure0
breast neoplasm0
stomatitis0
tachycardia0
vaginal hemorrhage0
weight gain0
uveitis0
neck rigidity0
vaginitis0
migraine0
bronchitis0
cataract0
sinus bradycardia0
vertigo0
viral infection0
liver function tests abnormal0
urticaria0
hyperchloremia0
tendinitis0
tenesmus0
abdominal pain upper0
tooth disorder0
myalgia0
dry skin0
urinary incontinence0
urinary tract infection0
sgot increased0
alkaline phosphatase increased0
eye pain0
dry mouth0
adenomas0
coronary artery disease0
cough0
cystitis0
cyst0
deafness0
dysphagia0
dermatitis0
contact dermatitis0
diabetes mellitus0
diverticulitis0
somnolence0
dysuria0
ear pain0
ecchymosis0
edema0
constipation0
conjunctivitis0
albuminuria0
alopecia0
anemia0
anorexia0
anxiety0
aortic valve incompetence0
arthralgia0
asthenia0
bacterial infections0
clotting0
moniliasis0
cellulitis0
cerebral infarction0
cerebrovascular disorder0
chest pain0
epicondylitis0
epistaxis0
eructation0
arthrosis0
kidney calculus0
labyrinthitis0
laryngitis0
leg cramps0
breast pain0
melena0
fungal infection0
nail disorder0
nasopharyngitis0
nervousness0
neuralgia0
gastroenteritis0
otitis media0
ovarian cyst0
influenza0
infection0
esophagitis0
fatigue0
vitreous floaters0
flushing0
gastritis0
glaucoma0
hematuria0
hemorrhoids0
hiatal hernia0
herpes simplex0
herpes zoster0
hypercholesterolemia0
hyperglycemia0
hypersensitivity0
hypokalemia0
palpitations0

Target

show target details
Uniprot ID:PGH2_HUMAN
Synonyms:
COX-2
Cyclooxygenase-2
PGH synthase 2
PGHS-2
PHS II
Prostaglandin G/H synthase 2
Prostaglandin H2 synthase 2
Prostaglandin-endoperoxide synthase 2
EC-Numbers:1.14.99.1
Organism:Homo sapiens
Human
PDB IDs:1V0X
Structure:
1V0X

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----
----
----
----
----
----
----
--0.52-
--2-
--2.2-
--6-
--6.8-
--35-
--36-
--40-
--50.7-
--54.0-
--56.7-
--60-
--63-
--65-
--68-
--70-
--70.0-
--70-
--79-
--80-
--110-
--120-
--230-
--330-
--336-
--350-
--500-
--530-
--540-
--600-
--800-
--1000-
--1100-
--1200-
--1300-
--2900-
--3600-

References:

015965713
11005360
Cyclooxygenase-2 inhibitor celecoxib: a possible cause of gastropathy and hypoprothrombinemia.. J D Linder; K E Mönkemüller; J V Davis; C M Wilcox (2000) Southern medical journal display abstract
Gastrointestinal side effects from nonsteroidal anti-inflammatory drugs (NSAIDs) result mainly from inhibition of the enzyme cyclooxygenase (COX)-1; it is responsible for the synthesis of prostaglandin E2, which leads to increased mucosal blood flow, increased bicarbonate secretion, and mucus production, thus protecting the gastrointestinal mucosa. In inflammation, COX-2 is induced, causing synthesis of the prostaglandins in conditions such as osteoarthritis and rheumatoid arthritis. Two NSAIDs (celecoxib and rofecoxib) with very high specificity for COX-2 and virtually no activity against COX-1 at therapeutic doses have been approved for clinical use. In trials of celecoxib and rofecoxib, only 0.02% of patients had clinically significant gastrointestinal bleeding, compared to a 1% to 2% yearly incidence of severe gastrointestinal side effects with NSAIDs. Our patient had arthritis of the hips and chronic atrial fibrillation and was on warfarin therapy for stroke prevention; less than a week after starting celecoxib therapy, gastrointestinal bleeding and hypoprothrombinemia occurred.
12483719
Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors.. Natsuko Kusunoki; Ryuta Yamazaki; Shinichi Kawai (2002) Arthritis and rheumatism display abstract
OBJECTIVE: Selective cyclooxygenase 2 (COX-2) inhibitors are now being used as antiinflammatory agents that cause fewer gastrointestinal complications, compared with other antiinflammatory drugs, in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether selective COX-2 inhibitors could induce apoptosis of RA synovial fibroblasts (RASFs). METHODS: RASFs were exposed to selective COX-2 inhibitors, i.e., celecoxib, etodolac, meloxicam, nimesulide, N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide, and rofecoxib, under various conditions. Cell proliferation and cell viability were assessed by incorporation of 5-bromo-2'-deoxyuridine and by the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt assay, respectively. Apoptosis was detected by identifying DNA fragmentation. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) was measured by the luciferase reporter gene assay with a PPAR response element-driven luciferase reporter plasmid and a PPARgamma expression plasmid. RESULTS: Celecoxib strongly inhibited the proliferation of RASFs, whereas other selective COX-2 inhibitors had little or no effect. In addition, celecoxib reduced the viability of RASFs by induction of apoptosis, in a concentration-dependent manner. This action was abolished by addition of caspase inhibitors. Interleukin-1beta had a weak enhancing effect on celecoxib-induced apoptosis in RASFs. In contrast, other selective COX-2 inhibitors at concentrations up to 100 microM did not induce apoptosis of RASFs. Indomethacin, a nonselective COX inhibitor, activated PPARgamma transcription, while celecoxib did not. CONCLUSION: Celecoxib suppressed the proliferation of RASFs by COX-2-independent and PPARgamma-independent induction of apoptosis. Although the mechanism involved remains unclear, celecoxib may have not only antiinflammatory activity, but also a disease-modifying effect on rheumatoid synovial proliferation.
14764122
A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy.. R S Pruthi; J E Derksen; D Moore (2004) BJU international display abstract
OBJECTIVES: To evaluate the efficacy of the cyclooxygenase (COX)-2 inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer after definitive radiation therapy (RT) or radical prostatectomy (RP), as recent evidence showed that COX-2 inhibitors have potent antitumour activity in prostate cancer both in vitro and in vivo but there are no human trials. PATIENTS AND METHODS: Twelve patients who had biochemical relapse after RT or RP were treated with celecoxib 200 mg twice daily. Follow-up PSA levels to assess efficacy were obtained at 3, 6 and 12 months after initiating treatment. Data were evaluated by calculating PSA doubling times and the slope of the curve of logPSA vs time, to assess rate of PSA rise before and after celecoxib treatment for each patient. Serum testosterone levels were also measured. RESULTS: Eight of the 12 patients had significant inhibition of their serum PSA levels after 3 months of treatment; five had a decline in their absolute PSA level and three a stabilization of the level. Of the remaining four patients, three had a marked decrease in their PSA doubling time, with a mean increase (i.e. slowing) of 3.1 times that before treatment. The short-term responses at 3 months also continued at 6 and 12 months. From the slope of log PSA vs time there was a significant flattening of the rate of PSA rise (P = 0.001). There was a significant change of patients with rapid doubling times towards slower doubling times or even stable/declining PSA values after treatment with celecoxib (P = 0.029). There was no significant change in testosterone levels, suggesting an androgen-independent mechanism. CONCLUSIONS: COX-2 inhibitors may have an effect on serum PSA levels in patients with biochemical progression after RT or RP. These results suggest that COX-2 inhibitors may help to delay or prevent disease progression in these patients, and thereby help extend the time until androgen deprivation therapy. Further study with more patients is currently underway to better evaluate the clinical potential of COX-2 inhibitors as an antitumour agents in prostate cancer.
15205346
From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors.. Jiuxiang Zhu; Jui-Wen Huang; Ping-Hui Tseng; Ya-Ting Yang; Joseph Fowble; Chung-Wai Shiau; Yeng-Jeng Shaw; Samuel K Kulp; Ching-Shih Chen (2004) Cancer research display abstract
The blockade of Akt activation through the inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1) represents a major signaling mechanism whereby celecoxib mediates apoptosis. Celecoxib, however, is a weak PDK-1 inhibitor (IC(50), 48 microM), requiring at least 30 microM to exhibit discernable effects on the growth of tumor cells in vitro. Here, we report the structure-based optimization of celecoxib to develop PDK-1 inhibitors with greater potency in enzyme inhibition and growth inhibition. Kinetics of PDK-1 inhibition by celecoxib with respect to ATP suggest that celecoxib derivatives inhibit PDK-1 by competing with ATP for binding, a mechanism reminiscent to that of many kinase inhibitors. Structure-activity analysis together with molecular modeling was used to generate compounds that were tested for their potency in inhibiting PDK-1 kinase activity and in inducing apoptosis in PC-3 prostate cancer cells. Docking of potent compounds into the ATP-binding site of PDK-1 was performed for lead optimization, leading to two compounds, OSU-03012 and OSU-03013, with IC(50) values in PDK-1 inhibition and apoptosis induction in the low microM range. Exposure of PC-3 cells to these agents led to Akt dephosphorylation and inhibition of p70 S6 kinase activity. Moreover, overexpression of constitutively active forms of PDK-1 and Akt partially protected OSU-03012-induced apoptosis. Screening in a panel of 60 cell lines and more extensive testing in PC-3 cells indicated that the mean concentration for total growth inhibition was approximately 3 microM for both agents. Considering the conserved role of PDK-1/Akt signaling in promoting tumorigenesis, these celecoxib analogs are of translational relevance for cancer prevention and therapy.
15256475
Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates activation of cigarette smoke-induced nuclear factor (NF)-kappaB by suppressing activation of IkappaBalpha kinase in human non-small cell lung carcinoma: correlation with suppression of cyclin D1, COX-2, and matrix metalloproteinase-9.. Shishir Shishodia; Bharat B Aggarwal (2004) Cancer research display abstract
Cigarette smoke (CS) has been linked to cardiovascular, pulmonary, and malignant diseases. CS-associated malignancies including cancers of the larynx, oral cavity, and pharynx, esophagus, pancreas, kidney, bladder, and lung; all are known to overexpress the nuclear factor-kappaB (NF-kappaB)-regulated gene products cyclin D1, cyclooxygenase (COX)-2, and matrix metalloprotease-9. Whether the COX-2 inhibitor, celecoxib, approved for the treatment of colon carcinogenesis and rheumatoid arthritis, affects CS-induced NF-kappaB activation is not known, although the role of NF-kappaB in regulation of apoptosis, angiogenesis, carcinogenesis, and inflammation is established. In our study, in which we examined DNA binding of NF-kappaB in human lung adenocarcinoma H1299 cells, we found that cigarette smoke condensate (CSC)-induced NF-kappaB activation was persistent up to 24 h, and celecoxib suppressed CSC-induced NF-kappaB activation. Celecoxib was effective even when administered 12 h after CSC treatment. This effect, however, was not cell type-specific. The activation of inhibitory subunit of NF-kappaB kinase (IkappaB), as examined by immunocomplex kinase assay, IkappaB phosphorylation, and IkappaB degradation was also inhibited. Celecoxib also abrogated CSC-induced p65 phosphorylation and nuclear translocation and NF-kappaB-dependent reporter gene expression. CSC-induced NF-kappaB reporter activity induced by NF-kappaB inducing kinase and IkappaB alpha kinase but not that activated by p65 was also blocked by celecoxib. CSC induced the expression of NF-kappaB-regulated proteins, COX-2, cyclin D1, and matrix metalloproteinase-9, and celecoxib abolished the induction of all three. The COX-2 promoter that is regulated by NF-kappaB was activated by CSC, and celecoxib suppressed its activation. Overall, our results suggest that chemopreventive effects of celecoxib may in part be mediated through suppression of NF-kappaB and NF-kappaB-regulated gene expression, which may contribute to its ability to suppress inflammation, proliferation, and angiogenesis.
16290146
Carbonic anhydrase inhibitors: Valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II "selective" inhibitor celecoxib.. Anna Di Fiore; Carlo Pedone; Katia D'Ambrosio; Andrea Scozzafava; Giuseppina De Simone; Claudiu T Supuran (2006) Bioorganic & medicinal chemistry letters display abstract
The high resolution X-ray crystal structure of the adduct of human carbonic anhydrase (CA, EC 4.2.1.1) isoform II (hCA II) with the clinically used painkiller valdecoxib, acting as a potent CA II and cyclooxygenase-2 (COX-2) inhibitor, is reported. The ionized sulfonamide moiety of valdecoxib is coordinated to the catalytic Zn(II) ion with a tetrahedral geometry. The phenyl-isoxazole moiety of the inhibitor fills the active site channel and interacts with the side chains of Gln92, Val121, Leu198, Thr200, and Pro202. Its 3-phenyl group is located into a hydrophobic pocket, simultaneously establishing van der Waals interactions with the aliphatic side chain of various hydrophobic residues (Val135, Ile91, Val121, Leu198, and Leu141) and a strong offset face-to-face stacking interaction with the aromatic ring of Phe131 (the chi1 angle of which is rotated about 90 degrees with respect to what was observed in the structure of the native enzyme and those of other sulfonamide complexes). Celecoxib, a structurally related COX-2 inhibitor for which the X-ray crystal structure was reported earlier, binds in a completely different manner to hCA II as compared to valdecoxib. Celecoxib completely fills the entire CA II active site, with its trifluoromethyl group in the hydrophobic part of the active site and the p-tolyl moiety in the hydrophilic one, not establishing any interaction with Phe131. In contrast to celecoxib, valdecoxib was rotated about 90 degrees around the chemical bond connecting the benzensulfonamide and the substituted isoxazole ring allowing for these multiple favorable interactions. These different binding modes allow for the further drug design of various CA inhibitors belonging to the benzenesulfonamide class.
17121918
Inhibition of 5-lipoxygenase by MK886 augments the antitumor activity of celecoxib in human colon cancer cells.. Fabio Cianchi; Camillo Cortesini; Lucia Magnelli; Elena Fanti; Laura Papucci; Nicola Schiavone; Luca Messerini; Alfredo Vannacci; Sergio Capaccioli; Federico Perna; Matteo Lulli; Valentina Fabbroni; Giuliano Perigli; Paolo Bechi; Emanuela Masini (2006) Molecular cancer therapeutics display abstract
Cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) are key enzymes involved in arachidonic acid metabolism. Their products, prostaglandins and leukotrienes, are involved in colorectal tumor development. We aimed at evaluating whether combined blocking of the COX-2 and 5-LOX pathways might have additive antitumor effects in colorectal cancer. The expression/activity of COX-2 and 5-LOX were assessed in 24 human colorectal cancer specimens. The effects of the COX-2 inhibitor celecoxib and the 5-LOX inhibitor MK886 on prostaglandin E(2) and cysteinyl leukotriene production, tumor cell proliferation, cell apoptosis, and Bcl-2/Bax expression were evaluated in the Caco-2 and HT29 colon cancer cells. We also investigated the effect of the enzymatic inhibition on mitochondrial membrane depolarization, one of the most important mechanisms involved in ceramide-induced apoptosis. Up-regulation of the COX-2 and 5-LOX pathways was found in the tumor tissue in comparison with normal colon mucosa. Inhibition of either COX-2 or 5-LOX alone resulted in activation of the other pathway in colon cancer cells. Combined treatment with 10 micromol/L celecoxib and MK886 could prevent this activation and had additive effects on inhibiting tumor cell proliferation, inducing cell apoptosis, decreasing Bcl-2 expression, increasing Bax expression, and determining mitochondrial depolarization in comparison with treatment with either inhibitor alone. The administration of the ceramide synthase inhibitor fumonisin B1 could prevent some of these antineoplastic effects. In conclusion, our study showed that inhibition of 5-LOX by MK886 could augment the antitumor activity of celecoxib in human colorectal cancer.
18552508
Celecoxib inhibits serum amyloid a-induced matrix metalloproteinase-10 expression in human endothelial cells.. Yulan Zhao; Shuli Zhou; Chew-Kiat Heng (2009) Journal of vascular research display abstract
BACKGROUND: Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated. METHODS AND RESULTS: From our time course microarray screening, SAA (20 microg/ml) was found to increase MMP-10 mRNA expression over time (4-48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E(2) (PGE(2)), as possible mediators of MMP-10 induction. Direct PGE(2) treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA. CONCLUSIONS: SAA induced MMP-10 expression and celecoxib prevented its induction. MMP-10 induction was at least partly mediated by PGE(2).
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