INT224723

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Context Info
Confidence 0.33
First Reported 2007
Last Reported 2007
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 10
Disease Relevance 11.14
Pain Relevance 3.76

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

peptidase activity (Metap2) cytoplasm (Metap2)
Anatomy Link Frequency
endothelial cells 2
synovium 1
Metap2 (Mus musculus)
Pain Link Frequency Relevance Heat
Arthritis 840 99.92 Very High Very High Very High
rheumatoid arthritis 460 99.40 Very High Very High Very High
Inflammation 150 93.12 High High
chemokine 80 90.32 High High
Inflammatory response 10 86.40 High High
cytokine 130 77.96 Quite High
cINOD 10 5.00 Very Low Very Low Very Low
Inflammatory stimuli 10 5.00 Very Low Very Low Very Low
imagery 10 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Arthritis 870 99.92 Very High Very High Very High
Rheumatoid Arthritis 470 99.40 Very High Very High Very High
Cancer 60 99.20 Very High Very High Very High
Disease 240 95.76 Very High Very High Very High
INFLAMMATION 170 93.12 High High
Immunization 50 92.52 High High
Sprains And Strains 10 92.16 High High
Necrosis 30 88.68 High High
Disease Progression 20 80.24 Quite High
Erythema 40 74.08 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In the present study we utilized CIA to investigate further the therapeutic potential in RA of PPI-2458, an irreversible MetAP-2 inhibitor based on the fumagillin class of compounds.
Negative_regulation (inhibitor) of MetAP-2 associated with rheumatoid arthritis and arthritis
1) Confidence 0.33 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.80 Pain Relevance 0.61
A reversible MetAP-2 inhibitor was also reported to lead to endothelial cell cycle arrest and to exhibit efficacy in a range of murine tumour models [17].
Negative_regulation (inhibitor) of MetAP-2 in endothelial cell associated with cancer
2) Confidence 0.33 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 0.65 Pain Relevance 0.09
Previous reports have shown that fumagillin and AGM-1470/TNP-470 primarily function by inhibiting cell proliferation [11,12], and it has therefore been suggested that irreversible inhibition of MetAP-2 catalytic activity accounts for at least part of the anticancer action of such compounds [13-15].
Negative_regulation (inhibition) of MetAP-2
3) Confidence 0.33 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 0.40 Pain Relevance 0.03
The response in chronic CIA to MetAP-2 inhibition indicates that PPI-2458 has therapeutic potential for future use in RA.


Negative_regulation (inhibition) of MetAP-2 associated with rheumatoid arthritis and arthritis
4) Confidence 0.25 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.36 Pain Relevance 0.58
Fumagillin and its analogues are reported to be potent, irreversible and selective inhibitors of MetAP-2 [29].
Negative_regulation (inhibitors) of MetAP-2
5) Confidence 0.25 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 0.99 Pain Relevance 0.25
These findings provide support for the concept that blockade of MetAP-2 may be an effective approach to treatment of RA.


Negative_regulation (blockade) of MetAP-2 associated with rheumatoid arthritis
6) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.42 Pain Relevance 0.54
Although we have not unequivocally demonstrated that angiogenesis is inhibited by PPI-2458 in vivo, the in vitro findings suggest that inhibition of MetAP-2 might translate to reduced blood vessel formation in arthritic synovium.
Negative_regulation (inhibition) of MetAP-2 in synovium associated with arthritis
7) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.08 Pain Relevance 0.60
Other MetAP-2 inhibitors have been described as inhibiting tumour growth in mice, and to induce accumulation in endothelial cells of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 [18].
Negative_regulation (inhibitors) of MetAP-2 in endothelial cells associated with cancer
8) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 0.83 Pain Relevance 0.19
We report that PPI-2458, an inhibitor of MetAP-2, not only inhibits acute CIA model but also has profound effect on the pathology of chronic CIA.
Negative_regulation (inhibitor) of MetAP-2 associated with arthritis
9) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.56 Pain Relevance 0.56
It has been reported that fumagillin and other molecules that may act by inhibiting MetAP-2 reduce arthritis in animal models.
Negative_regulation (inhibiting) of MetAP-2 associated with arthritis
10) Confidence 0.24 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2246249 Disease Relevance 1.04 Pain Relevance 0.31

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