Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDS00041

Target Information
NameProstaglandin G/H synthase 2    
Type of targetSuccessful target    
Cyclooxygenase -2    
Cyclooxygenase 2    
Heme-protein prostaglandin G/H synthase    
PGH synthase 2    
PHS II    
Prostaglandin H2 synthase 2    
Prostaglandin-endoperoxide synthase 2    
DiseaseAbdominal aortic aneurysm    [1]
Adenomatous polyposis    [2]
Alzheimer's disease    [3]
Analgesics    [4][5]
Arthritis    [6]
Bladder cancer    [7]
Breast cancer    [8][9]
Cancer, unspecific    [10]
Carcinoma in situ, unspecified    [11]
Carpal tunnel syndrome    [12]
Colorectal cancer    [13][14]
Dysmenorrhea, unspecified    [15]
Endometriosis    [16]
Genitourinary tumors    [17]
Gestational hypertension    [18]
Inflammation    [19]
Inflammatory diseases    [3][20]
Lung cancer    [21]
Malignant mesothelioma    [22]
Meningioma    [23]
Myocardial infarction    [24][25]
Oropharyngeal squamous cell carcinoma    [26]
Osteoarthritis    [15]
Pain, unspecified    [4][5]
Pathological angiogenesis    [27]
Peutz-Jeghers syndrome    [28][29]
Prostate cancer    [30][31]
Pyresis    [5]
Renal cell carcinoma    [32]
Rheumatoid arthritis, unspecified    [33]
Stroke    [34]
Vascular lesion regression    [35]
CelecoxibApprovedRheumatoid arthritis and osteoarthritis[37][38][4][15][33][15][39][2]
EtoricoxibApprovedRheumatoid arthritis and osteoarthritis[42][43]
KetoprofenApprovedRheumatoid arthritis and pain[46]
LumiracoxibApprovedKnee osteoarthritis [47]
Mefenamic acidApprovedRheumatoid arthritis and osteoarthritis[48]
NabumetoneApprovedRheumatoid arthritis and osteoarthritis[50][51]
NaproxenApprovedPain and Rheumatoid arthritis[52][40]
Niflumic AcidApprovedRheumatoid arthritis[53]
PhenylbutazoneApprovedChronic pain[54]
TenoxicamApprovedRheumatoid arthritis and osteoarthritis[56][57]
Tiaprofenic acidApprovedPain[58]
TolmetinApprovedRheumatoid arthritis and osteoarthritis[44]
ValdecoxibApprovedOsteoarthritis and rheumatoid arthritis[59]
ONO-2506Phase III completedStroke[60]
CelecoxibPhase IIIPain[61][62][38]
GSK-644784Suspended in Phase II in GSK 2006 ReportNeuropathic pain[63]
GW-406381Suspended in Phase III in GSK 2006 ReportOsteoarthritis, Neuropathic pain[63]
NimesulidePreclinicalAcute pain; fever; osteoarthritis; dysmenorrhea[60]
RPR 200765APreclinicalRheumatoid arthritis[6]
BioChemical ClassOxidoreductases acting on paired donors    
EC NumberEC
PathwayArachidonic acid metabolism
Pathways in cancer
Small cell lung cancer
VEGF signaling pathway
UniProt IDP35354
PDB Structure1V0X.    
FunctionMay have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.    
Related US Patent6,204,387
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Flufenamic Acid[72]
Mefenamic acid[48]
Nectamazin C[81]
Niflumic Acid[53]
Prostaglandin G2[74]
RPR 200765A[6]
SB 202190[86]
SB 203580[19]
SB 239063[87]
Tiaprofenic acid[58]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
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Ref 2The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 2000 Sep 15;60(18):5040-4. To Reference
Ref 3Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol Aging. 2002 May-Jun;23(3):327-34. To Reference
Ref 4A randomized, clinical trial comparing oral celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 600 mg for acute pain. Acad Emerg Med. 2003 Jan;10(1):22-30. To Reference
Ref 5Analysis of prostaglandin G/H synthase-2 inhibition using peroxidase-induced luminol luminescence. Anal Biochem. 1998 Nov 15;264(2):216-21. To Reference
Ref 6The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy. Bioorg Med Chem. 2001 Feb;9(2):537-54. To Reference
Ref 7Enhanced expression of cyclooxygenase-2 in high grade human transitional cell bladder carcinomas. Am J Pathol. 2000 Jul;157(1):29-35. To Reference
Ref 8Cyclooxygenase-2: a potential target in breast cancer. Semin Oncol. 2004 Feb;31(1 Suppl 3):64-73. To Reference
Ref 9Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer. 2001 Jun;8(2):97-114. To Reference
Ref 10COX-2 inhibitors in cancer treatment and prevention, a recent development. Anticancer Drugs. 2002 Feb;13(2):127-37. To Reference
Ref 11Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. Clin Cancer Res. 2000 Jun;6(6):2424-30. To Reference
Ref 12COX-2 up-regulation in idiopathic carpal tunnel syndrome. Plast Reconstr Surg. 2003 Dec;112(7):1807-14. To Reference
Ref 13COX-2 selective inhibition reverses the trophic properties of gastrin in colorectal cancer. Br J Cancer. 2002 Aug 27;87(5):574-9. To Reference
Ref 14Cyclooxygenase-2 expression in right- and left-sided colon cancer: a rationale for optimization of cyclooxygenase-2 inhibitor therapy. Clin Colorectal Cancer. 2004 Feb;3(4):243-7. To Reference
Ref 15Valdecoxib (Pharmacia). Curr Opin Investig Drugs. 2002 Feb;3(2):240-5. To Reference
Ref 16Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis. Zentralbl Gynakol. 2003 Jul-Aug;125(7-8):247-51. To Reference
Ref 17Cyclooxygenase-2 as a potential target in the prevention and treatment of genitourinary tumors: a review. J Urol. 2003 Jun;169(6):2352-9. To Reference
Ref 18Aspirin during pregnancy. Indications and modalities of prescription after the publication of the later trials. Presse Med. 1996 Jan 6-13;25(1):31-6. To Reference
Ref 19Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology. 2000 May;47(2-3):185-201. To Reference
Ref 20Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J Biol Chem. 2004 May 21;279(21):22727-37. Epub 2004 Mar 12. To Reference
Ref 21Lung cancer and cyclooxygenase-2. Ann Thorac Surg. 2003 Oct;76(4):1327-35. To Reference
Ref 22Cyclooxygenase-2 expression is a novel prognostic factor in malignant mesothelioma. Clin Cancer Res. 2002 Jun;8(6):1857-62. To Reference
Ref 23Cyclooxygenase-2 (COX-2) expression in human meningioma as a function of tumor grade. Am J Clin Oncol. 2003 Aug;26(4):S98-102. To Reference
Ref 24Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in the mouse. Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1416-24. Epub 2003 Dec 11. To Reference
Ref 25Inhibition of cyclooxygenase-2 improves cardiac function in myocardial infarction. Biochem Biophys Res Commun. 2000 Jul 5;273(2):772-5. To Reference
Ref 26Prognostic significance of cyclooxygenase-2 in oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2004 Mar 1;10(5):1678-84. To Reference
Ref 27Cyclooxygenase-2: a therapeutic target in angiogenesis. Trends Mol Med. 2003 Feb;9(2):73-8. To Reference
Ref 28Induction of cyclooxygenase-2 in a mouse model of Peutz-Jeghers polyposis. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12327-32. Epub 2002 Sep 6. To Reference
Ref 29Correlation of staining for LKB1 and COX-2 in hamartomatous polyps and carcinomas from patients with Peutz-Jeghers syndrome. J Histochem Cytochem. 2003 Dec;51(12):1665-72. To Reference
Ref 30Induction of apoptosis by cyclooxygenase-2 inhibitors in prostate cancer cell lines. Int J Urol. 2001 Jul;8(7):S35-9. To Reference
Ref 31HER2 and COX2 expression in human prostate cancer. Eur J Cancer. 2004 Jan;40(1):50-5. To Reference
Ref 32Significance of COX-2 expression in human renal cell carcinoma cell lines. Int J Cancer. 2004 Mar 1;108(6):825-32. To Reference
Ref 33Clinical experience with cyclooxygenase-2 inhibitors. Rheumatology (Oxford). 2002 Apr;41 Supp 1:16-22; discussion 35-42. To Reference
Ref 34Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1294-9. To Reference
Ref 35Antisense strategies to inhibit restenosis. Antisense Nucleic Acid Drug Dev. 1999 Oct;9(5):487-92. To Reference
Ref 36Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators. J Med Chem. 2006 Dec 28;49(26):7588-91. To Reference
Ref 37Celecoxib enhanced the sensitivity of cancer cells to anticancer drugs by inhibition of the expression of P-glycoprotein through a COX-2-Independent Manner. J Cell Biochem. 2009 Jun 26. [Epub ahead of print] To Reference
Ref 38Mini Rev Med Chem. 2007 Nov;7(11):1108-19.Privileged structures: a useful concept for the rational design of new lead drug candidates. To Reference
Ref 39New and future drug therapies for rheumatoid arthritis. Rheumatology (Oxford). 2000 Jun;39 Suppl 1:36-42. To Reference
Ref 40Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice. J Am Dent Assoc. 2001 Apr;132(4):451-6. To Reference
Ref 41Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis. Intern Med. 2007;46(13):1055-8. Epub 2007 Jul 2. To Reference
Ref 42The effect of newer anti-rheumatic drugs on osteogenic cell proliferation: an in-vitro study. J Orthop Surg Res. 2009 May 26;4:17. To Reference
Ref 43Antiinflammatory effects of etoricoxib alone and combined with NSAIDs in LPS-induced reactive arthritis. Inflamm Res. 2008 Dec;57(12):586-92. To Reference
Ref 44Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44. Epub 2009 Apr 18. To Reference
Ref 45The cyclooxygenase inhibitor ibuprofen and the FLAP inhibitor MK886 inhibit pancreatic carcinogenesis induced in hamsters by transplacental exposure to ethanol and the tobacco carcinogen NNK. J Cancer Res Clin Oncol. 2002 Oct;128(10):525-32. Epub 2002 Aug 29. To Reference
Ref 46Probing the skin permeation of fish oil/EPA and ketoprofen-3. Effects on epidermal COX-2 and LOX. Prostaglandins Leukot Essent Fatty Acids. 2007 Jun;76(6):357-62. Epub 2007 Jun 25. To Reference
Ref 47Dissociation of airway inflammation and hyperresponsiveness by cyclooxygenase inhibition in allergen challenged mice. Eur Respir J. 2009 Jul;34(1):200-8. Epub 2009 Feb 27. To Reference
Ref 48Systematic pharmacological approach to the characterization of NSAIDs. Prostaglandins Leukot Essent Fatty Acids. 1998 Jul;59(1):55-62. To Reference
Ref 49Variability in the response to cyclooxygenase inhibitors: toward the individualization of nonsteroidal anti-inflammatory drug therapy. J Investig Med. 2009 Aug;57(6):709-16. To Reference
Ref 50Novel determination of nabumetone, a cox-2 inhibitor precursor via its 4-carboxyl-2,6-dinitrobenzene diazonium (CDNBD) derived AZO dye. Afr J Med Med Sci. 2007 Sep;36(3):249-57. To Reference
Ref 51Cyclo-oxygenase 2 inhibitor, nabumetone, inhibits proliferation in chronic myeloid leukemia cell lines. Leuk Lymphoma. 2005 May;46(5):753-6. To Reference
Ref 52Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD). Expert Opin Biol Ther. 2009 May;9(5):649-57. To Reference
Ref 53Rat ovulation, implantation and decidualization are severely compromised by COX-2 inhibitors. Front Biosci. 2007 May 1;12:3333-42. To Reference
Ref 54COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res. 2005 Oct;52(4):302-6. To Reference
Ref 55The analgesic actions of centrally administered celecoxib are mediated by endogenous opioids. Pain. 2009 Mar;142(1-2):94-100. Epub 2009 Jan 30. To Reference
Ref 56The use and safety profile of non-steroidal antiinflammatory drugs among Turkish patients with osteoarthritis. Turk J Gastroenterol. 2005 Sep;16(3):138-42. To Reference
Ref 57A randomized crossover trial of tenoxicam compared with rofecoxib for postoperative dental pain control. Anaesth Intensive Care. 2004 Dec;32(6):770-4. To Reference
Ref 58Effects of tiaprofenic acid on the concentration and metabolism of proteoglycans in normal and degenerating canine articular cartilage. J Clin Pharmacol. 1990 Sep;30(9):808-14. To Reference
Ref 59Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and safety. To Reference
Ref 60Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. To Reference
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Ref 64Nat Rev Drug Discov. 2003 Jan;2(1):38-51.Knockouts model the 100 best-selling drugs--will they model the next 100? To Reference
Ref 65The effect of the selective cyclooxygenase-2 inhibitor rofecoxib on human colorectal cancer liver metastases. Gastroenterology. 2003 Sep;125(3):716-29. To Reference
Ref 66Bioorg Med Chem Lett. 2009 Mar 15;19(6):1650-3. Epub 2009 Feb 7.Inhibitory activity of prostaglandin E2 production by the synthetic 2'-hydroxychalcone analogues: Synthesis and SAR study. To Reference
Ref 67J Nat Prod. 2005 Oct;68(10):1514-8.Selective cyclooxygenase-2 inhibitors from Calophyllum membranaceum. To Reference
Ref 68Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
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Ref 70Current status of COX-2 inhibitors. Mini Rev Med Chem. 2008 Jan;8(1):73-90. To Reference
Ref 71Bioorg Med Chem Lett. 1999 Aug 2;9(15):2207-12.SAR in the alkoxy lactone series: the discovery of DFP, a potent and orally active COX-2 inhibitor. To Reference
Ref 72Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51. To Reference
Ref 73Bioorg Med Chem Lett. 2009 Aug 1;19(15):4504-8. Epub 2009 Feb 26.Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors. To Reference
Ref 74Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 75Bioorg Med Chem Lett. 1999 Jan 18;9(2):151-6.Substituted heterocyclic analogs as selective COX-2 inhibitors in the flosulide class. To Reference
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Ref 77Bioorg Med Chem. 2010 Jan 15;18(2):597-604. Epub 2009 Dec 6.Discovery of 3-(4-bromophenyl)-6-nitrobenzo[1.3.2]dithiazolium ylide 1,1-dioxide as a novel dual cyclooxygenase/5-lipoxygenase inhibitor that also inhibits tumor necrosis factor-alpha production. To Reference
Ref 78Inhibition of cell cycle oscillation of DNA replication by a selective inhibitor of the cdc2 kinase family, butyrolactone I, in Xenopus egg extracts. Biochem Biophys Res Commun. 1994 Jan 28;198(2):536-45. To Reference
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Ref 83J Med Chem. 2007 Dec 13;50(25):6367-82. Epub 2007 Nov 10.Structure-based design, synthesis, and biological evaluation of indomethacin derivatives as cyclooxygenase-2 inhibiting nitric oxide donors. To Reference
Ref 84J Med Chem. 2005 Oct 20;48(21):6523-43.Designed multiple ligands. An emerging drug discovery paradigm. To Reference
Ref 85Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness. Clin Exp Immunol. 2002 Feb;127(2):337-43. To Reference
Ref 86A selective inhibitor of p38 MAP kinase, SB202190, induced apoptotic cell death of a lipopolysaccharide-treated macrophage-like cell line, J774.1. Biochim Biophys Acta. 2000 Oct 18;1502(2):207-23. To Reference
Ref 87SB-239063, a potent and selective inhibitor of p38 map kinase: preclinical pharmacokinetics and species-specific reversible isomerization. Pharm Res. 2001 Sep;18(9):1336-44. To Reference
Ref 88Bioorg Med Chem. 2010 Mar 15;18(6):2204-18. Epub 2010 Feb 8.In silico search for multi-target anti-inflammatories in Chinese herbs and formulas. To Reference
Ref 89J Med Chem. 1998 Mar 26;41(7):1124-37.New cyclooxygenase-2/5-lipoxygenase inhibitors. 2. 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations of the dihydrobenzofuran ring. To Reference
Ref 90Bioorg Med Chem Lett. 2009 Aug 1;19(15):4509-14. Epub 2009 Feb 27.Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach. To Reference
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Ref 92J Med Chem. 2002 Mar 28;45(7):1511-7.4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1). To Reference
Ref 93Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB. Cancer Res. 2000 Apr 1;60(7):1805-9. To Reference


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