Target Information

Target General Information

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Target ID

T03403 (Former ID: TTDS00039)

Target Name

Prostaglandin G/H synthase (COX)

Synonyms

Prostaglandin-endoperoxide synthase; Prostaglandin H2 synthase; PHS; PGHS; PGH synthase; Cyclooxygenase; COX

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Gene Name

PTGS1; PTGS2

Target Type

Successful target

[1]

Disease

[+] 13 Target-related Diseases

Cerebral ischaemia [ICD-11: 8B1Z]

Hyper-lipoproteinaemia [ICD-11: 5C80]

Inflammatory spondyloarthritis [ICD-11: FA92]

Inherited coagulation factor deficiency [ICD-11: 3B14]

Joint pain [ICD-11: ME82]

Migraine [ICD-11: 8A80]

Myocardial infarction [ICD-11: BA41-BA43]

Osteoarthritis [ICD-11: FA00-FA05]

Otitis media [ICD-11: AA80-AB0Z]

Pain [ICD-11: MG30-MG3Z]

Postoperative inflammation [ICD-11: 1A00-CA43]

Rheumatoid arthritis [ICD-11: FA20]

Spinal pain [ICD-11: ME84]

Function

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. PTGS1 is involved in the constitutive production of prostanoids in particular in the stomach and platelets. It is a key step in the generation of prostaglandins in gastric epithelial cells and the generation of thromboxane A2 (TXA2) in platelets. PTGS2 is 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.

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BioChemical Class

Paired donor oxygen oxidoreductase

UniProt ID

PGH1_HUMAN ; PGH2_HUMAN

Sequence

MSRSLLLWFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL

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Drugs and Modes of Action

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Approved Drug(s)

[+] 16 Approved Drugs

Aceclofenac

Drug Info

Approved

Inflammation

[5], [7]

Ampiroxicam

Drug Info

Approved

Inflammation

[5]

Amtolmetin guacil

Drug Info

Approved

Inflammation

[5]

Asasantin

Drug Info

Approved

Cerebrovascular ischaemia

[8]

Aspirin

Drug Info

Approved

Pain

[9], [8]

Dexibuprofen

Drug Info

Approved

Ankylosing spondylitis

[5]

Diclofenac

Drug Info

Approved

Osteoarthritis

[5]

Fenoprofen

Drug Info

Approved

Rheumatoid arthritis

[10], [11]

Fosfosal

Drug Info

Approved

Pain

[5]

Icosapent

Drug Info

Approved

Thrombin deficiency

[5], [12]

Ketorolac

Drug Info

Approved

Postoperative inflammation

[5]

Loxoprofen gel

Drug Info

Approved

Inflammation

[5], [13]

Meclofenamic acid

Drug Info

Approved

Ankylosing spondylitis

[5], [14], [15]

Morniflumate

Drug Info

Approved

Otitis media

[5]

Nepafenac

Drug Info

Approved

Osteoarthritis

[5], [16], [17]

Oxaprozin

Drug Info

Approved

Rheumatoid arthritis

[5]

Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

K-103-IP

Drug Info

Phase 3

Pain

[19]

BN82451

Drug Info

Phase 2

Parkinson disease

[20]

NCX 1022

Drug Info

Phase 2

Atopic dermatitis

[21]

NCX-4016

Drug Info

Phase 2

Inflammation

[22]

TZI-41078

Drug Info

Phase 2

Arthritis

[23]

4-aminosalicylate sodium

Drug Info

Phase 1

Inflammatory bowel disease

[25]

Discontinued Drug(s)

[+] 16 Discontinued Drugs

Droxicam

Drug Info

Withdrawn from market

Inflammation

[26]

Zomepirac

Drug Info

Withdrawn from market

Pain

[5]

Bermoprofen

Drug Info

Discontinued in Preregistration

Inflammation

[27]

Pirazolac

Drug Info

Discontinued in Preregistration

Inflammation

[28]

KC-764

Drug Info

Discontinued in Phase 3

Platelet aggregation disorder

[29]

Benzydamine

Drug Info

Discontinued in Phase 2

Chemotherapy or radiotherapy-induced mucositis

[31]

D-7193

Drug Info

Discontinued in Phase 2

Immune System disease

[32]

FS-205-397

Drug Info

Discontinued in Phase 2

Pain

[33]

NCX-701

Drug Info

Discontinued in Phase 2

Pain

[34]

D-1367

Drug Info

Discontinued in Phase 1

Arthritis

[35]

Eltenac

Drug Info

Discontinued in Phase 1

Arthritis

[36]

F-11105

Drug Info

Discontinued in Phase 1

Asthma

[37]

NMI-1182

Drug Info

Terminated

Inflammation

[40]

RP-66364

Drug Info

Terminated

Inflammation

[41]

S-14080

Drug Info

Terminated

Inflammation

[42]

WY-28342

Drug Info

Terminated

Rheumatoid arthritis

[43]

Mode of Action

[+] 3 Modes of Action

Modulator

[+] 24 Modulator drugs

Aceclofenac

Drug Info

[5], [44]

Ampiroxicam

Drug Info

[5], [45]

Amtolmetin guacil

Drug Info

[5], [46]

Dexibuprofen

Drug Info

[5], [48]

Diclofenac

Drug Info

[1], [5]

Fosfosal

Drug Info

[51], [52]

Morniflumate

Drug Info

[5], [58]

K-103-IP

Drug Info

[19]

NCX 1022

Drug Info

[61]

TZI-41078

Drug Info

[5], [23]

4-aminosalicylate sodium

Drug Info

[62]

Droxicam

Drug Info

[63]

Zomepirac

Drug Info

[5], [64]

Bermoprofen

Drug Info

[65]

Pirazolac

Drug Info

[66]

KC-764

Drug Info

[5], [67]

D-7193

Drug Info

[68]

FS-205-397

Drug Info

[5], [69]

NCX-701

Drug Info

[70], [71]

D-1367

Drug Info

[72]

Eltenac

Drug Info

[73]

RP-66364

Drug Info

[75]

S-14080

Drug Info

[76]

WY-28342

Drug Info

[77]

Inhibitor

[+] 13 Inhibitor drugs

Asasantin

Drug Info

[8]

Aspirin

Drug Info

[8], [47]

Fenoprofen

Drug Info

[49], [50]

Ketorolac

Drug Info

[54]

Loxoprofen gel

Drug Info

[5], [55]

Meclofenamic acid

Drug Info

[56], [57]

Nepafenac

Drug Info

[5], [59]

Oxaprozin

Drug Info

[49]

BN82451

Drug Info

[60]

NCX-4016

Drug Info

[8]

Benzydamine

Drug Info

[31]

F-11105

Drug Info

[68]

NMI-1182

Drug Info

[74]

Binder

[+] 1 Binder drugs

Icosapent

Drug Info

[53]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. Urol Res. 2000 Dec;28(6):376-82.

REF 2

The Diversion of Ultram, Ultracet, and generic tramadol HCL. J Addict Dis. 2006;25(2):53-8.

REF 3

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5239).

REF 4

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018337.

REF 5

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 6

ClinicalTrials.gov (NCT00997750) Efficacy and Safety of Lornoxicam in Patients With Acute Coronary Syndrome. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT01912066) A Multicenter, Double Blinded, Randomized, Parallel Assignment Study to Demonstrate the Efficacy of DA9601. U.S. National Institutes of Health.

REF 8

Emerging drugs in peripheral arterial disease. Expert Opin Emerg Drugs. 2006 Mar;11(1):75-90.

REF 9

REF 10

REF 11

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 072267.

REF 12

ClinicalTrials.gov (NCT00692718) N-3 Fatty Acids for the Prevention of Atrial Fibrillation in Patients With Acute Heart Failure. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT00994461) Study Of Celecoxib In Healthy Subjects. U.S. National Institutes of Health.

REF 14

REF 15

Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium. Clin J Pain. 1991;7 Suppl 1:S44-8.

REF 16

REF 17

2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).

REF 18

ClinicalTrials.gov (NCT00541489) Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Hip. U.S. National Institutes of Health.

REF 19

ClinicalTrials.gov (NCT02089425) An Efficacy and Safety Study for the Treatment of Mild to Moderate Acute Pain Associated With Ankle Strain or Sprain.. U.S. National Institutes of Health.

REF 20

ClinicalTrials.gov (NCT02231580) Study Exploring Safety, Pharmacokinetic and Pharmacodynamic of BN82451 in Male Huntington's Disease Patients. U.S. National Institutes of Health.

REF 21

Clinical pipeline report, company report or official report of NicOx SA.

REF 22

Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016). J Pharmacol Exp Ther. 2005 Dec;315(3):1331-7.

REF 23

Hydroxylamine analogs of 2,6-di-t-butylphenols: dual inhibitors of cyclooxygenase and 5-lipoxygenase or selective 5-lipoxygenase inhibitors. Bioorg Med Chem. 1995 Apr;3(4):403-10.

REF 24

Analgetic activity of SK&F 105809, a dual inhibitor of arachidonic acid metabolism. Agents Actions Suppl. 1991;32:113-7.

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022712)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003115)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000932)

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000980)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001148)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027456)

REF 31

Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007192)

REF 33

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003851)

REF 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014096)

REF 35

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005889)

REF 36

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003785)

REF 37

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010557)

REF 38

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000953)

REF 39

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003826)

REF 40

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020060)

REF 41

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003795)

REF 42

S14080, a peripheral analgesic acting by release of an endogenous circulating opioid-like substance. Br J Pharmacol. 1995 Jan;114(2):303-8.

REF 43

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005582)

REF 44

Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35.

REF 45

Premedication with cyclooxygenase-2 inhibitor meloxicam reduced postoperative pain in patients after oral surgery. Int J Oral Maxillofac Surg. 2006 Jul;35(7):613-7.

REF 46

Gastrointestinal safety of amtolmetin guacyl in comparison with celecoxib in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2005 Nov-Dec;23(6):809-18.

REF 47

Cyclooxygenase inhibitors: instrumental drugs to understand cardiovascular homeostasis and arterial thrombosis. Cardiovasc Hematol Disord Drug Targets. 2008 Dec;8(4):268-77.

REF 48

Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. Int J Clin Pharmacol Ther. 2003 Apr;41(4):153-64.

REF 49

The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.

REF 50

Immunomodulatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) at the clinically available doses. Arch Pharm Res. 2007 Jan;30(1):64-74.

REF 51

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 52

Pharmacological study of 2-phosphonoxybenzoic acid (fosfosal), a new analgesic drug. Arzneimittelforschung. 1980;30(7):1091-8.

REF 53

Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003 Mar;44(3):479-86.

REF 54

Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.

REF 55

Comparative study of the clinical efficacy of the selective cyclooxygenase-2 inhibitor celecoxib compared with loxoprofen in patients with frozen shoulder. Mod Rheumatol. 2014 Jan;24(1):144-9.

REF 56

Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7.

REF 57

Pharmacology of prostaglandin endoperoxide synthase isozymes-1 and -2. Ann N Y Acad Sci. 1994 Apr 18;714:136-42.

REF 58

Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions. 1991 Jul;33(3-4):233-9.

REF 59

Topical nepafenac inhibits ocular neovascularization. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):409-15.

REF 60

Emerging drug therapies in Huntington's disease. Expert Opin Emerg Drugs. 2009 Jun;14(2):273-97.

REF 61

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis. Br J Pharmacol. 2004 Nov;143(5):618-25.

REF 62

5-aminosalicylic acid mediates expression of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase to suppress colorectal tumorigenesis. Anticancer Res. 2012 Apr;32(4):1193-202.

REF 63

Pharmacokinetic profile of droxicam. Eur J Rheumatol Inflamm. 1991;11(4):10-4.

REF 64

Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia. J Cereb Blood Flow Metab. 1986 Dec;6(6):691-702.

REF 65

Prolongation of antipyretic action and reduction of gastric ulcerogenicity in the rat by controlled-release granules of bermoprofen, a new nonsteroidal anti-inflammatory drug. J Pharm Sci. 1991 Sep;80(9):876-80.

REF 66

Differential dosing study of pirazolac, a new non-steroidal anti-inflammatory agent, in patients with rheumatoid arthritis. Curr Med Res Opin. 1985;9(8):542-7.

REF 67

Clinical and preclinical pharmacology of KC-764, a novel antiplatelet agent. Nihon Rinsho. 1992 Feb;50(2):379-84.

REF 68

US patent application no. 6,673,908, Tumor necrosis factor receptor 2.

REF 69

FS 205-397: a new antipyretic analgesic with a paracetamol-like profile of activity but lack of acute hepatotoxicity in mice. Life Sci. 1988;43(11):905-12.

REF 70

Antinociceptive effects of NCX-701 (nitro-paracetamol) in neuropathic rats: enhancement of antinociception by co-administration with gabapentin. Br J Pharmacol. 2009 September; 158(2): 601-609.

REF 71

Nitroparacetamol (NCX-701) and pain: first in a series of novel analgesics. CNS Drug Rev. 2007 Fall;13(3):279-95.

REF 72

US patent application no. 2007,0072,861, Method of using cyclooxygenase-2 inhibitors in the prevention of cardiovascular disorders.

REF 73

Effect of eltenac in horses with induced endotoxaemia. Equine Vet J Suppl. 2000 Jun;(32):26-31.

REF 74

NMI-1182, a gastro-protective cyclo-oxygenase-inhibiting nitric oxide donor. Inflammopharmacology. 2005;12(5-6):521-34.

REF 75

WO patent application no. 1997,0297,75, Compositions comprising a cyclooxygenase-2 inhibitor and a leukotriene b4 receptor antagonist.

REF 76

US patent application no. 7,022,689, 5-amidino-n-(2-aminophenethyl)-n-hydroxy-benzenesulffonamide derivative, medical composition containing the same, pharmaceutical use thereof and intermediate therefor.

REF 77

Synthesis and antiinflammatory activity of certain 5,6,7,8-tetrahydroquinolines and related compounds. J Med Chem. 1995 Apr 28;38(9):1473-81.

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