INT9053

Context Info Confidence 0.58 First Reported 1983 Last Reported 2010 Negated 0 Speculated 1 Reported most in Abstract Documents 97 Total Number 98 Disease Relevance 40.34 Pain Relevance 29.94

cytosol (ALOX5) nuclear envelope (ALOX5) small molecule metabolic process (ALOX5) oxidoreductase activity (ALOX5) nucleus (ALOX5) cytoplasm (ALOX5)

Anatomy Link Frequency platelet 4 macrophages 2 fibroblast 2 leukocytes 2 neutrophils 2 ALOX5 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 753 100.00 COX-2 inhibitor 149 100.00 aspirin 172 99.76 diclofenac 8 99.76 licofelone 179 99.74 Opioid 6 99.72 cINOD 400 99.52 Pain 143 99.52 Inflammatory mediators 175 99.20 COX2 33 99.18

Disease Link Frequency Relevance Heat INFLAMMATION 1126 100.00 Apoptosis 163 99.76 Adenocarcinoma 60 99.68 Pain 165 99.52 Colon Cancer 52 99.48 Alzheimer's Dementia 1 98.82 Atherosclerosis 93 98.80 Asthma 240 98.40 Disease 418 97.96 Cancer 416 97.22

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Inhibition of the lipoxygenase might be an advantageous adjunct to the effect of the Non Steroidal Anti-Inflammatory Drugs.

Negative_regulation (Inhibition) of lipoxygenase associated with inflammation

1) Confidence 0.58 Published 1985 Journal Prostaglandins Section Abstract Doc Link 3001832 Disease Relevance 0.97 Pain Relevance 0.94

This explains the efforts to obtain drugs able to inhibit both 5-lipoxygenase and cyclooxygenases: the so-called dual acting anti-inflammatory drugs.

Negative_regulation (inhibit) of 5-lipoxygenase associated with inflammation and cinod

2) Confidence 0.57 Published 2002 Journal Curr. Med. Chem. Section Abstract Doc Link 12733982 Disease Relevance 0.79 Pain Relevance 0.82

Dual COX/5-LOX (cyclooxygenase/5-lipoxygenase) inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases.

Negative_regulation (inhibitors) of 5-LOX associated with inflammation, cinod, cox-2 inhibitor and disease

3) Confidence 0.57 Published 2003 Journal Eur J Med Chem Section Abstract Doc Link 12932896 Disease Relevance 0.36 Pain Relevance 0.36

The balanced inhibitors of 5-lipoxygenase (5-LOX) and of cyclooxygenase (both types 1 and 2) block the formation of all the enzymatically arachidonic acid-derived metabolites, both prostaglandins (like COX inhibitors) and leukotrienes (LT); these drugs have been shown to possess a very good anti-inflammatory efficacy without serious side effects.

Negative_regulation (inhibitors) of 5-LOX associated with inflammation

4) Confidence 0.57 Published 2003 Journal Prostaglandins Other Lipid Mediat. Section Abstract Doc Link 14518558 Disease Relevance 0.69 Pain Relevance 0.45

Spice phenolics inhibit human PMNL 5-lipoxygenase.

Negative_regulation (inhibit) of 5-lipoxygenase

5) Confidence 0.57 Published 2004 Journal Prostaglandins Leukot. Essent. Fatty Acids Section Title Doc Link 15120715 Disease Relevance 0 Pain Relevance 0.15

These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX) with selectivity for the COX-2 isoform.

Negative_regulation (inhibitors) of 5-LOX

6) Confidence 0.57 Published 1998 Journal J. Med. Chem. Section Abstract Doc Link 9544212 Disease Relevance 0.17 Pain Relevance 0.17

The products generated by the 5-lipoxygenase pathway (leukotrienes) are particularly important in inflammation: indeed, leukotrienes increase microvascular permeability and are potent chemotactic agents; moreover, inhibition of 5-lipoxygenase indirectly reduces the expression of TNF-alpha (a cytokine that plays a key role in inflammation).

Negative_regulation (inhibition) of 5-lipoxygenase associated with inflammation and cytokine

7) Confidence 0.57 Published 2002 Journal Curr. Med. Chem. Section Abstract Doc Link 12733982 Disease Relevance 0.68 Pain Relevance 0.84

These approaches include: apoptosis inhibitors; inhibitors of APP processing (prolyl endopeptidase (EC 3.4.21.26) inhibitors, gamma-secretase inhibitors, and inhibitors of amyloid aggregation); and, prostaglandin formation (COX-2 and COX/5-LO inhibitors).

Negative_regulation (inhibitors) of 5-LO associated with alzheimer's dementia and apoptosis

8) Confidence 0.57 Published 1998 Journal IDrugs Section Abstract Doc Link 18465621 Disease Relevance 0.84 Pain Relevance 0.08

Antileukotriene therapies inhibit synthesis of leukotrienes through ALOX5 inhibition or by blocking the cysteinyl leukotriene receptor.

Negative_regulation (inhibition) of ALOX5

9) Confidence 0.51 Published 2010 Journal Indian Journal of Human Genetics Section Body Doc Link PMC3009420 Disease Relevance 0.48 Pain Relevance 0.05

Then during 3 days the patients took 75-100 mg indomethacin which dose was quite sufficient for inhibition of the activity of arachidonic acid cyclooxygenase.

Negative_regulation (inhibition) of arachidonic acid cyclooxygenase

10) Confidence 0.46 Published 1985 Journal Neurol. Neurochir. Pol. Section Abstract Doc Link 3937967 Disease Relevance 0.31 Pain Relevance 0.39

Simulations on widely used anti-inflammatory inhibitors, including 5-LOX inhibitor, COX-2 inhibitor, and a combination of the two, were performed (Figure 3).

Negative_regulation (inhibitor) of 5-LOX associated with inflammation and cox-2 inhibitor

11) Confidence 0.44 Published 2007 Journal PLoS Computational Biology Section Body Doc Link PMC1829479 Disease Relevance 0.32 Pain Relevance 0.26

We then did further simulation on the combination of 5-LOX inhibitor and COX inhibitor.

Negative_regulation (inhibitor) of 5-LOX

12) Confidence 0.44 Published 2007 Journal PLoS Computational Biology Section Body Doc Link PMC1829479 Disease Relevance 0.36 Pain Relevance 0.33

Results in our studies suggest that the combination of the COX-2 inhibitor and the 5-LOX inhibitor would have better treatment.

Negative_regulation (inhibitor) of 5-LOX associated with cox-2 inhibitor

13) Confidence 0.44 Published 2007 Journal PLoS Computational Biology Section Body Doc Link PMC1829479 Disease Relevance 0.52 Pain Relevance 0.40

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 5-LO associated with cinod

14) Confidence 0.42 Published 2009 Journal Curr. Med. Chem. Section Abstract Doc Link 19519380 Disease Relevance 0.43 Pain Relevance 0.79

Other possible reasons for the enhanced antinociceptive activity by coadministering minocycline and indomethacin could have been due to the inhibition of COX enzyme activity by indomethacin and inhibition of 5-lipoxygenase activity by minocycline.

Negative_regulation (inhibition) of 5-lipoxygenase associated with antinociceptive

15) Confidence 0.42 Published 2010 Journal BMC Musculoskelet Disord Section Body Doc Link PMC3009629 Disease Relevance 0.86 Pain Relevance 0.80

In a study with a 5-lipoxygenase inhibitor, response to treatment was shown to be related to genotype; individuals having alleles associated with low transcriptional activity of the gene showed little or no response to treatment with a 5-lipoxygenase inhibitor [27].

Negative_regulation (inhibitor) of 5-lipoxygenase

16) Confidence 0.42 Published 2002 Journal Respir Res Section Body Doc Link PMC64808 Disease Relevance 0 Pain Relevance 0.05

In a study with a 5-lipoxygenase inhibitor, response to treatment was shown to be related to genotype; individuals having alleles associated with low transcriptional activity of the gene showed little or no response to treatment with a 5-lipoxygenase inhibitor [27].

Negative_regulation (inhibitor) of 5-lipoxygenase

17) Confidence 0.42 Published 2002 Journal Respir Res Section Body Doc Link PMC64808 Disease Relevance 0 Pain Relevance 0.04

Although it is tempting to equate in vitro COX-2/COX-1 and 5-LOX inhibition to overall in vivo safety, the data do not support this approach.

Negative_regulation (inhibition) of 5-LOX

18) Confidence 0.42 Published 2006 Journal Vet. Clin. North Am. Small Anim. Pract. Section Abstract Doc Link 16984827 Disease Relevance 0.09 Pain Relevance 0.25

Dual COX/5-LOX (cyclooxygenase/5-lipoxygenase) inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors for the treatment of inflammatory diseases.

Negative_regulation (inhibitors) of 5-LOX associated with inflammation, cinod, cox-2 inhibitor and disease

19) Confidence 0.41 Published 2003 Journal Eur J Med Chem Section Abstract Doc Link 12932896 Disease Relevance 0.36 Pain Relevance 0.36

In addition, characterization of variation in the ALOX5 gene was different (number of promoter Sp1 binding motifs versus SNPs within LD blocks across the entire ALOX5 gene).

Negative_regulation (blocks) of ALOX5

20) Confidence 0.40 Published 2010 Journal Mediators of Inflammation Section Body Doc Link PMC2878676 Disease Relevance 0.75 Pain Relevance 0.04

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