INT143925

Context Info Confidence 0.42 First Reported 2007 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 18 Total Number 18 Disease Relevance 10.50 Pain Relevance 5.18

isomerase activity (Ptges) nucleus (Ptges) cytoplasm (Ptges)

Anatomy Link Frequency monocytes 1 cardiovascular system 1 fat 1 muscle 1 superior 1 Ptges (Mus musculus)

Pain Link Frequency Relevance Heat Inflammation 76 100.00 Pain 22 99.78 licofelone 16 98.80 cINOD 34 96.92 COX-2 inhibitor 38 91.40 Inflammatory response 2 89.08 cytokine 3 86.60 Multiple sclerosis 47 67.92 Arthritis 1 61.28 Demyelination 30 51.32

Disease Link Frequency Relevance Heat INFLAMMATION 93 100.00 Multiple Sclerosis 32 99.42 Natriuresis 1 99.32 Pain 19 98.96 Disease 20 98.72 Syndrome 3 98.36 Pleurisy 6 98.28 Pressure And Volume Under Development 5 97.60 Adenoma 2 97.28 Cancer 6 96.68

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Effects of AF3442 [N-(9-ethyl-9H-carbazol-3-yl)-2-(trifluoromethyl)benzamide], a novel inhibitor of human microsomal prostaglandin E synthase-1, on prostanoid biosynthesis in human monocytes in vitro.

Negative_regulation (inhibitor) of prostaglandin E synthase in monocytes

1) Confidence 0.42 Published 2010 Journal Biochem. Pharmacol. Section Title Doc Link 19925781 Disease Relevance 0.18 Pain Relevance 0.09

Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease.

Negative_regulation (inhibition) of prostaglandin E synthase associated with pain, inflammation and disease

2) Confidence 0.41 Published 2008 Journal J. Intern. Med. Section Title Doc Link 18410593 Disease Relevance 1.08 Pain Relevance 0.61

Mice lacking mPGES-1 exhibit blunted natriuretic response paralleled with remarkably suppressed nitric oxide production, leading to salt-sensitive hypertension.

Negative_regulation (lacking) of mPGES-1 associated with natriuresis and hypertension

3) Confidence 0.41 Published 2007 Journal Kidney Int. Section Abstract Doc Link 17495855 Disease Relevance 0.53 Pain Relevance 0.21

However, we found that mPGES-1 deficiency was associated with a disorganized vascular pattern within primary adenomas as determined by CD31 immunostaining.

Negative_regulation (deficiency) of mPGES-1 associated with adenoma

4) Confidence 0.25 Published 2008 Journal Cancer Res. Section Abstract Doc Link 18451151 Disease Relevance 0.94 Pain Relevance 0.07

The potential efficacy of selective inhibition of mPGES-1 in preventing or retarding aneurysm formation warrants further investigation.

Negative_regulation (inhibition) of mPGES-1

5) Confidence 0.20 Published 2008 Journal Circulation Section Body Doc Link 18285567 Disease Relevance 0 Pain Relevance 0

Male mice deficient in both mPGES-1 and LDLR (mPGES-1(-/-) LDLR(-/-)) and littermate LDLR(-/-) mice were initiated on a high-fat diet at 6 months of age, followed 1 week later by continuous infusion of angiotensin II (1 microg/kg per minute) for an additional 4 weeks.

Negative_regulation (deficient) of mPGES-1 in fat

6) Confidence 0.15 Published 2008 Journal Circulation Section Body Doc Link 18285567 Disease Relevance 0.36 Pain Relevance 0

Indeed, the failure of PGES?

Negative_regulation (failure) of PGES

7) Confidence 0.13 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2585850 Disease Relevance 1.29 Pain Relevance 0.06

EAE is less severe in mice that lack the microsomal PGE synthase 1 (MPGES-1) gene that codes for the enzyme that synthesizes PGE2 from COX-derived PGH2 [40].

Negative_regulation (lack) of MPGES-1 associated with multiple sclerosis

8) Confidence 0.08 Published 2010 Journal J Neuroinflammation Section Body Doc Link PMC2873241 Disease Relevance 1.23 Pain Relevance 0.35

Inhibitors of microsomal PGE synthase-1 (mPGES-1) are being developed for relief of pain and interest has focused on their potential impact on the cardiovascular system.

Negative_regulation (Inhibitors) of mPGES-1 in cardiovascular system associated with pain

9) Confidence 0.08 Published 2008 Journal J. Intern. Med. Section Abstract Doc Link 18410593 Disease Relevance 0.96 Pain Relevance 0.40

Pain relief seems likely to be a nuanced indication for mPGES-1 inhibitors, but they have therapeutic potential in syndromes of cardiovascular inflammation, cancer and perhaps in neurodegenerative disease.

Negative_regulation (inhibitors) of mPGES-1 associated with pain, inflammation, cancer, syndrome and neurodegenerative disease

10) Confidence 0.08 Published 2008 Journal J. Intern. Med. Section Abstract Doc Link 18410593 Disease Relevance 1.31 Pain Relevance 0.53

We conclude that licofelone suppresses inflammatory PGE(2) formation preferentially by inhibiting mPGES-1 at concentrations that do not affect COX-2, implying an attractive and thus far unique molecular pharmacological dynamics as inhibitor of COX-1, the 5-lipoxygenase pathway, and of mPGES-1.

Negative_regulation (inhibitor) of mPGES-1 associated with inflammation and licofelone

11) Confidence 0.02 Published 2008 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 18550688 Disease Relevance 0.10 Pain Relevance 0.48

Selective inhibition of mPGES-1 will allow for intact baseline PGE2 production as well as intact production of other PG important for muscle regeneration and, ultimately, constitute a more preferable anti-inflammatory treatment than the currently used systemic GCs.

Negative_regulation (inhibition) of mPGES-1 in muscle associated with inflammation

12) Confidence 0.02 Published 2008 Journal Annals of the Rheumatic Diseases Section Body Doc Link PMC2582339 Disease Relevance 0.65 Pain Relevance 0.16

We conclude that licofelone suppresses inflammatory PGE(2) formation preferentially by inhibiting mPGES-1 at concentrations that do not affect COX-2, implying an attractive and thus far unique molecular pharmacological dynamics as inhibitor of COX-1, the 5-lipoxygenase pathway, and of mPGES-1.

Negative_regulation (inhibiting) of mPGES-1 associated with inflammation and licofelone

13) Confidence 0.02 Published 2008 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 18550688 Disease Relevance 0.10 Pain Relevance 0.56

Selective inhibition of pro-inflammatory prostaglandin (PG)E(2) formation via microsomal PGE(2) synthase-1 (mPGES-1) might be superior over inhibition of all cyclooxygenase (COX)-derived products by non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs.

Negative_regulation (inhibition) of mPGES-1 in superior associated with inflammation and cinod

14) Confidence 0.01 Published 2009 Journal Bioorg. Med. Chem. Section Abstract Doc Link 19884011 Disease Relevance 0.20 Pain Relevance 0.24

Ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 7a) inhibits human mPGES-1 in a cell-free assay (IC(50)=0.6 microM) as well as in intact A549 cells (IC(50)=2 microM), and suppressed PGE(2) pleural levels in rat carrageenan-induced pleurisy.

Negative_regulation (inhibits) of mPGES-1 in A549 associated with pleurisy

15) Confidence 0.01 Published 2009 Journal Bioorg. Med. Chem. Section Abstract Doc Link 19884011 Disease Relevance 0.48 Pain Relevance 0.31

Together, based on the select and potent inhibition of mPGES-1 and 5-lipoxygenase, benzo[g]indol-3-carboxylates possess potential as novel anti-inflammatory drugs with a valuable pharmacological profile.

Negative_regulation (inhibition) of mPGES-1 associated with inflammation and cinod

16) Confidence 0.01 Published 2009 Journal Bioorg. Med. Chem. Section Abstract Doc Link 19884011 Disease Relevance 0.61 Pain Relevance 0.31

Based on that background two different approaches were pursued in the search for GI sparing NSAIDs: a) modification of classical NSAIDs by associating them with phospholipids, cyclodextrins, or chemical moieties that release gastroprotective mediators and b) defining novel targets as well as developing new compounds like dual COX/5-LO or mPGES-1 inhibitors.

Negative_regulation (inhibitors) of mPGES-1 associated with cinod

17) Confidence 0.00 Published 2009 Journal Curr. Med. Chem. Section Abstract Doc Link 19519380 Disease Relevance 0.43 Pain Relevance 0.79

Progress in designing molecules that can selectively inhibit mPGES-1 is reviewed.

Negative_regulation (inhibit) of mPGES-1

18) Confidence 0.00 Published 2009 Journal Expert Opin. Ther. Targets Section Body Doc Link 19530988 Disease Relevance 0.08 Pain Relevance 0

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