INT13406

Context Info Confidence 0.57 First Reported 1991 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 25 Total Number 25 Disease Relevance 10.61 Pain Relevance 6.36

cytosol (CASP1) peptidase activity (CASP1) signal transduction (CASP1) intracellular (CASP1) cytoplasm (CASP1)

Anatomy Link Frequency cerebrospinal fluid 2 chondrocytes 1 articular 1 monocytes 1 endothelial cell 1 CASP1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 136 100.00 antagonist 62 100.00 Dynorphin 5 100.00 cINOD 23 99.84 Gabapentin 2 99.50 anticonvulsant 5 98.90 cytokine 84 98.88 aspirin 36 98.40 anesthesia 1 97.88 Infliximab 2 97.32

Disease Link Frequency Relevance Heat INFLAMMATION 181 99.96 Disease 73 99.24 Apoptosis 62 98.88 Epilepsy 14 97.44 Osteoarthritis 7 96.68 Neurological Disease 4 96.08 Cryopyrin-associated Periodic Syndromes 6 94.48 Convulsion 6 93.32 Death 47 92.96 Patent Foramen Ovale 13 91.60

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

ICE/caspase 1 inhibitors and IL-1beta receptor antagonists as potential therapeutics in epilepsy.

Negative_regulation (inhibitors) of ICE/caspase associated with epilepsy, inflammation and antagonist

1) Confidence 0.57 Published 2010 Journal Curr Opin Investig Drugs Section Title Doc Link 20047158 Disease Relevance 1.38 Pain Relevance 0.42

Taken together, these data indicate that incubating human monocytes with NCX-4016 causes intracellular NO formation and suppresses IL-1beta and IL-18 processing by inhibiting caspase-1 activity.

Negative_regulation (inhibiting) of caspase-1 in monocytes

2) Confidence 0.56 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.15 Pain Relevance 0.19

Caspase-1 inhibition is a new, cycloxygenase-independent antiinflammatory mechanism of NO-aspirin.

Negative_regulation (inhibition) of Caspase-1 associated with aspirin and inflammation

3) Confidence 0.56 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.25 Pain Relevance 0.20

Inhibitors of TACE and Caspase-1 as anti-inflammatory drugs.

Negative_regulation (Inhibitors) of Caspase-1 associated with inflammation and cinod

4) Confidence 0.47 Published 2005 Journal Curr. Med. Chem. Section Title Doc Link 16378499 Disease Relevance 1.17 Pain Relevance 0.75

This review summarizes the proof-of-principle evidence, obtained in experimental disease models, demonstrating the anticonvulsant activity of specific anti-inflammatory drugs, such as inhibitors of IL-1-converting enzyme/caspase 1 and antagonists of IL-1beta receptors.

Negative_regulation (inhibitors) of IL-1-converting associated with inflammation, antagonist, cinod, anticonvulsant and disease

5) Confidence 0.42 Published 2010 Journal Curr Opin Investig Drugs Section Abstract Doc Link 20047158 Disease Relevance 1.38 Pain Relevance 0.44

This effect is largely owing to post-translational nitrosation and therefore inactivation of cysteine proteases, such as the interleukin (IL)-1beta converting enzyme (ICE/caspase-1) involved in pro-cytokine processing.

Negative_regulation (inactivation) of ICE associated with cytokine

6) Confidence 0.42 Published 2001 Journal Trends Immunol. Section Abstract Doc Link 11323270 Disease Relevance 0.18 Pain Relevance 0.66

The inhibition of caspase-1 by NCX-4016 was reversible by the addition of DTT, which is consistent with S-nitrosylation as the mechanism of caspase-1 inhibition.

Negative_regulation (inhibition) of caspase-1

7) Confidence 0.41 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.21 Pain Relevance 0.38

NCX-4016, similar to the NO donor S-nitroso-N-acetyl-D-L-penicillamine, inhibited caspase-1 activity with an EC(50) of approximately 20 microM.

Negative_regulation (inhibited) of caspase-1

8) Confidence 0.41 Published 2000 Journal J. Immunol. Section Abstract Doc Link 11046058 Disease Relevance 0.21 Pain Relevance 0.37

In this article, we describe the identification of the protein bikunin as an endogenous, competitive inhibitor of a dynorphin-converting enzyme in human cerebrospinal fluid.

Negative_regulation (inhibitor) of dynorphin-converting enzyme in cerebrospinal fluid associated with dynorphin

9) Confidence 0.27 Published 2006 Journal FEBS J. Section Abstract Doc Link 17087727 Disease Relevance 0 Pain Relevance 0.49

In contrast, human cerebrospinal fluid dynorphin-converting enzyme (hCSFDCE) is inhibited only moderately by these inhibitors.

Negative_regulation (inhibited) of cerebrospinal fluid dynorphin-converting enzyme in cerebrospinal fluid associated with dynorphin

10) Confidence 0.24 Published 1991 Journal J. Enzym. Inhib. Section Abstract Doc Link 1669830 Disease Relevance 0 Pain Relevance 0.22

Twenty-four hours later, the transcription of all components remained lower and the decrease of the caspase-1 level became also significant when compared to the level measured in the non-exposed control cells (Figure 5B).

Negative_regulation (decrease) of caspase-1

11) Confidence 0.23 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2526096 Disease Relevance 0 Pain Relevance 0

The caspase-1 inhibitor was effective in reducing relative levels of secreted 17-kDa IL-1?

Negative_regulation (inhibitor) of caspase-1

12) Confidence 0.23 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2906308 Disease Relevance 0 Pain Relevance 0.08

Instead of getting primed for the recognition of altered intracellular structures potentially generated as a consequence of UV irradiation, downregulation of ASC, Cardinal, and caspase-1 might prevent the triggering of the innate immunity system by limiting the available adaptor and enzyme molecules.

Negative_regulation (downregulation) of caspase-1

13) Confidence 0.23 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2526096 Disease Relevance 0.37 Pain Relevance 0

Caspase-1 inhibition significantly attenuated all pathways resulting in IL-1?

Negative_regulation (inhibition) of Caspase-1

14) Confidence 0.17 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2906308 Disease Relevance 0.13 Pain Relevance 0.26

The caspase-1 inhibitor YVAD significantly attenuated IL-1?

Negative_regulation (inhibitor) of caspase-1

15) Confidence 0.17 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2906308 Disease Relevance 0 Pain Relevance 0.10

The orally available pro-drug VX-765, a potent, selective inhibitor of caspase-1, blocked IL-1?

Negative_regulation (inhibitor) of caspase-1

16) Confidence 0.15 Published 2010 Journal F1000 Med Rep Section Body Doc Link PMC2948378 Disease Relevance 0.37 Pain Relevance 0.03

Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.

Negative_regulation (inhibition) of IL-1beta-induced in chondrocytes associated with inflammation and apoptosis

17) Confidence 0.11 Published 2009 Journal Arthritis Res. Ther. Section Title Doc Link 19889203 Disease Relevance 0.66 Pain Relevance 0.47

Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis.

Negative_regulation (suppresses) of interleukin-1beta-induced in articular associated with inflammation, apoptosis and osteoarthritis

18) Confidence 0.08 Published 2008 Journal Biochem. Pharmacol. Section Title Doc Link 18606398 Disease Relevance 1.18 Pain Relevance 0.41

Antagonists of caspase-1 activity, acetyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and

Negative_regulation (Antagonists) of caspase-1 in CMK associated with antagonist

19) Confidence 0.08 Published 2006 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC1510947 Disease Relevance 0.91 Pain Relevance 0.09

In contrast, inhibition of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of an inhibitor of caspase-1) has no effect on disease onset but extends survival by increasing the duration of symptomatic disease.

Negative_regulation (inhibitor) of caspase-1 associated with disease, apoptosis and gabapentin

20) Confidence 0.07 Published 1998 Journal J. Inherit. Metab. Dis. Section Abstract Doc Link 9728338 Disease Relevance 1.12 Pain Relevance 0.26

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