INT17848

Context Info Confidence 0.46 First Reported 1991 Last Reported 2010 Negated 7 Speculated 1 Reported most in Abstract Documents 70 Total Number 86 Disease Relevance 32.10 Pain Relevance 20.60

small molecule metabolic process (PTGS2) endoplasmic reticulum (PTGS2) enzyme binding (PTGS2) protein complex (PTGS2) cytoplasm (PTGS2) lipid binding (PTGS2)

Anatomy Link Frequency macrophages 1 NB-4 1 liver 1 colon 1 platelet 1 PTGS2 (Homo sapiens)

Pain Link Frequency Relevance Heat cINOD 171 100.00 cytokine 65 100.00 COX2 53 100.00 Inflammatory response 30 100.00 cOX1 4 100.00 Acute pain 2 100.00 diclofenac 12 99.98 aspirin 60 99.84 Inflammation 256 99.82 Pain 53 99.82

Disease Link Frequency Relevance Heat INFLAMMATION 359 100.00 Cancer 198 100.00 Pain 52 100.00 Myocardial Infarction 17 99.98 Multiple Myeloma 18 99.92 Apoptosis 84 99.90 Disease 118 99.68 Pressure And Volume Under Development 21 99.68 Death 21 99.66 Cv General 3 Under Development 4 99.66

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The potential for similar interactions with cyclooxygenase-2-specific inhibitors has not been fully explored.

cyclooxygenase-2-specific Binding (interactions) of

1) Confidence 0.46 Published 2001 Journal Am J Ther Section Abstract Doc Link 11304662 Disease Relevance 0.42 Pain Relevance 0.17

In addition, molecular modeling and docking of the tested compounds into cyclooxygenase II complexed with its bound inhibitor indomethacin (4COX) using molsoft icm 3.4-8C program was performed in order to predict the affinity and orientation of the synthesized compounds at the active site.

cyclooxygenase II Binding (complexed) of

2) Confidence 0.44 Published 2009 Journal Bioorg. Med. Chem. Section Abstract Doc Link 19527932 Disease Relevance 0.34 Pain Relevance 0.52

The other two structures namely PGFS and PGIS were added to make the dataset of 7649 structures in which four of them were known to bind PGH2.

PGH2 Binding (bind) of

3) Confidence 0.43 Published 2010 Journal BMC Bioinformatics Section Body Doc Link PMC3009524 Disease Relevance 0 Pain Relevance 0

These latter conclusions are based on the findings that the nonsteroidal anti-inflammatory drug diclofenac binds a single monomer of native huPGHS-2, having an unmodified Ser530 to inhibit the enzyme, and that diclofenac inhibits PGH(2) but not 15-hydroperoxyeicosatraenoic acid formation by acetylated huPGHS-2.

huPGHS-2 Binding (binds) of associated with inflammation, cinod and diclofenac

4) Confidence 0.42 Published 2010 Journal Mol. Pharmacol. Section Abstract Doc Link 20194532 Disease Relevance 0.18 Pain Relevance 0.44

Although the substrate PGH2, the ligand and its interactions with the protein were not taken into account during any of the computational steps performed by MultiBind, it never-the-less detected the key residues thought to be involved in the catalytic mechanism and superimposed the ligand molecules to similar locations in space, supporting the correctness of the alignment.

PGH2 Binding (interactions) of

5) Confidence 0.38 Published 2010 Journal BMC Bioinformatics Section Body Doc Link PMC3009524 Disease Relevance 0 Pain Relevance 0

distance from the bound PGH2 and Ligand, it was found that common amino acid residues participated in the binding of PGH2 to the synthases in the docked model and the ligand in the crystal structure obtained from PDB Among the common residues, the cofactors GSH, NADP and HEME involved in the catalytic mechanism of the synthases PGDS (GSH) [12], PGFS (NADP) [14] and PGIS (HEME) [15] respectively are also shown in Figure 1.

PGH2 Binding (bound) of

6) Confidence 0.38 Published 2010 Journal BMC Bioinformatics Section Body Doc Link PMC3009524 Disease Relevance 0 Pain Relevance 0

Convergence seems to be limited to similarity in the ability to bind PGH2 specifically and may not extend to the precise way in which this is achieved as indicated by the lack of similarity which can be characterized as a PGH2 binding site.

PGH2 Binding (bind) of

7) Confidence 0.38 Published 2010 Journal BMC Bioinformatics Section Body Doc Link PMC3009524 Disease Relevance 0 Pain Relevance 0

Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids.

cyclooxygenase-2 homodimer Binding (acetylation) of associated with aspirin

8) Confidence 0.37 Published 2010 Journal Mol. Pharmacol. Section Title Doc Link 20194532 Disease Relevance 0.12 Pain Relevance 0.47

Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells.

PGHS-2 Binding (Characterization) of associated with cox2 and osteogenic sarcomas

9) Confidence 0.37 Published 1997 Journal Inflamm. Res. Section Title Doc Link 9085144 Disease Relevance 0.41 Pain Relevance 0.41

Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis.

Cyclooxygenase 2 Binding (associated) of in liver associated with cox2

10) Confidence 0.37 Published 2002 Journal Int. J. Cancer Section Abstract Doc Link 12115513 Disease Relevance 0.38 Pain Relevance 0.26

While preliminary evidence has supported novel roles for these drugs in ankylosing spondylitis and in cancer prevention, accumulating evidence shows that some cyclooxygenase-2 and perhaps all nonsteroidal anti-inflammatory drugs are associated with cardiovascular toxicity.

cyclooxygenase-2 Binding (associated) of

11) Confidence 0.36 Published 2006 Journal Curr Opin Rheumatol Section Body Doc Link 16582683 Disease Relevance 0 Pain Relevance 0

BACKGROUND: Lumiracoxib (Prexige; Novartis Pharma AG, Basel, Switzerland) is a cyclooxygenase-2 selective inhibitor associated with improved gastrointestinal safety compared with nonsteroidal anti-inflammatory drugs, in patients with osteoarthritis.

cyclooxygenase-2 Binding (associated) of associated with inflammation, cinod and osteoarthritis

12) Confidence 0.36 Published 2004 Journal Aliment. Pharmacol. Ther. Section Abstract Doc Link 15153172 Disease Relevance 0.34 Pain Relevance 0.18

To summarize the evidence from published observational studies on the risk of myocardial infarction associated with both traditional NSAIDs (tNSAIDs) and selective inhibitors of cyclooxygenase-2 (Coxibs), the authors conducted a systematic review of cohort and case-control studies on NSAIDs and myocardial infarction published between 2000 and 2005.

cyclooxygenase-2 Binding (associated) of associated with cinod and myocardial infarction

13) Confidence 0.36 Published 2006 Journal Basic Clin. Pharmacol. Toxicol. Section Abstract Doc Link 16611201 Disease Relevance 0.65 Pain Relevance 0.56

However, less is known about how the risk of hypertension is associated with cyclooxygenase 2 selective inhibitors (coxibs), especially celecoxib, the only coxib remaining on the market.

cyclooxygenase 2 Binding (associated) of associated with pressure and volume under development and cox2

14) Confidence 0.36 Published 2007 Journal Ann Pharmacother Section Abstract Doc Link 17488830 Disease Relevance 0.46 Pain Relevance 0.22

arachidonic acid by the catalytic activities of the cyclooxygenase-2 (Cox-2)

Cox-2 Binding (acid) of

15) Confidence 0.36 Published 2008 Journal PPAR Research Section Body Doc Link PMC2408681 Disease Relevance 0.28 Pain Relevance 0.03

BACKGROUND: Licofelone, a potent antiinflammatory agent has been reported to interfere with the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) signaling pathways with few side-effects.

cyclooxygenase-2 Binding (interfere) of associated with inflammation and licofelone

16) Confidence 0.36 Published 2007 Journal Anticancer Res. Section Abstract Doc Link 17695530 Disease Relevance 0.17 Pain Relevance 0.27

Recent concerns regarding potential cardiovascular toxicities associated with cox-2 selective inhibitors may favor non-selective NSAID/PPI co-therapy as the preferred choice.

cox-2 Binding (associated) of associated with cinod

17) Confidence 0.36 Published 2006 Journal J Pain Palliat Care Pharmacother Section Abstract Doc Link 17182503 Disease Relevance 0.16 Pain Relevance 0.81

Molecular modelling of the differential interaction between several non-steroidal anti-inflammatory drugs and human prostaglandin endoperoxide H synthase-2 (h-PGHS-2).

PGHS-2 Binding (interaction) of associated with inflammation, cinod and cox2

18) Confidence 0.36 Published 2002 Journal J. Mol. Graph. Model. Section Title Doc Link 11858641 Disease Relevance 0.19 Pain Relevance 0.39

Our results indicate no strong association between the four most frequent PTGS2 SNPs and the risk of breast cancer.

PTGS2 Neg (no) Binding (association) of associated with breast cancer

19) Confidence 0.35 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2992523 Disease Relevance 0.39 Pain Relevance 0

Taken together, the results appear to indicate no association between PTGS2 SNPs (in their most frequent haplotypes) and the risk of breast cancer.

PTGS2 Neg (no) Binding (association) of associated with breast cancer

20) Confidence 0.35 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2992523 Disease Relevance 0.41 Pain Relevance 0

General Comments

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