INT145299

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Context Info
Confidence 0.48
First Reported 2007
Last Reported 2009
Negated 1
Speculated 0
Reported most in Body
Documents 25
Total Number 25
Disease Relevance 17.66
Pain Relevance 7.13

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

cytoskeleton (Jak3) intracellular (Jak3) kinase activity (Jak3)
cytoplasm (Jak3)
Anatomy Link Frequency
cartilage 2
T cell 2
osteoclast 1
mast cells 1
Jak3 (Mus musculus)
Pain Link Frequency Relevance Heat
endometriosis 27 99.88 Very High Very High Very High
rheumatoid arthritis 307 99.42 Very High Very High Very High
Inflammation 381 99.28 Very High Very High Very High
cytokine 245 98.68 Very High Very High Very High
antagonist 25 94.64 High High
Arthritis 572 93.64 High High
pain pelvic 6 87.12 High High
Dismenorea 6 86.60 High High
Hyperalgesia 3 83.84 Quite High
Pain 3 83.16 Quite High
Disease Link Frequency Relevance Heat
Endometriosis 30 99.88 Very High Very High Very High
Rheumatoid Arthritis 307 99.42 Very High Very High Very High
INFLAMMATION 364 99.28 Very High Very High Very High
Organ Transplantation 40 99.24 Very High Very High Very High
Disease 303 98.64 Very High Very High Very High
Toxicity 20 98.00 Very High Very High Very High
Autoimmune Disease 130 97.96 Very High Very High Very High
Arthritis 594 97.68 Very High Very High Very High
Hypersensitivity 87 97.52 Very High Very High Very High
Targeted Disruption 37 96.08 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
An inhibitor of Janus kinase 3 (Jak3) was also found to show selective inhibition on purified ?
Negative_regulation (inhibitor) of Jak3
1) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604888 Disease Relevance 0.06 Pain Relevance 0.09
An inhibitor of Janus kinase 3 (Jak3) was also found to show selective inhibition on purified ?
Negative_regulation (inhibitor) of Janus kinase 3
2) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604888 Disease Relevance 0.06 Pain Relevance 0.09
We hypothesize that JAK3 inhibitors, especially JANEX-1, may prove useful to prevent or alleviate the symptoms of EMS.
Negative_regulation (inhibitors) of JAK3 associated with endometriosis
3) Confidence 0.43 Published 2007 Journal Am. J. Reprod. Immunol. Section Abstract Doc Link 17631002 Disease Relevance 2.00 Pain Relevance 0.65
JANEX-1/WHI-P131 is a rationally designed novel JAK3 inhibitor with potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile.
Negative_regulation (inhibitor) of JAK3 associated with staphylococcus infection, colitis, toxicity, inflammation, burns and peritonitis
4) Confidence 0.43 Published 2007 Journal Am. J. Reprod. Immunol. Section Abstract Doc Link 17631002 Disease Relevance 2.15 Pain Relevance 0.77
Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1.
Negative_regulation (inhibitor) of janus kinase 3 in mast cells associated with endometriosis
5) Confidence 0.38 Published 2007 Journal Am. J. Reprod. Immunol. Section Title Doc Link 17631002 Disease Relevance 1.83 Pain Relevance 0.92
This labeling was prevented by the imatinib extract and the Jak3 inhibitor, but not by a transition-state analogue inhibitor (that is, directed to the active site).
Neg (not) Negative_regulation (inhibitor) of Jak3
6) Confidence 0.35 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2604888 Disease Relevance 0 Pain Relevance 0.03
CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis.
Negative_regulation (inhibitor) of Janus kinase 3 in T cell associated with cytokine
7) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2374467 Disease Relevance 0.35 Pain Relevance 0.20
CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5–15 mg/kg/day following disease induction.
Negative_regulation (inhibitor) of JAK3 associated with disease
8) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2374467 Disease Relevance 0.79 Pain Relevance 0.29
The potential for CP-690550 to attenuate multiple cytokines associated with rheumatoid arthritis by virtue of its ability to inhibit JAK3 may provide improved efficacy vs a single agent.
Negative_regulation (inhibit) of JAK3 associated with rheumatoid arthritis and cytokine
9) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374467 Disease Relevance 0.57 Pain Relevance 0.41
CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis.
Negative_regulation (inhibitor) of JAK3 in T cell associated with cytokine
10) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Abstract Doc Link PMC2374467 Disease Relevance 0.41 Pain Relevance 0.20
CP-690550, a potent inhibitor of JAK3, reduced the clinical and histological manifestations of joint inflammation, including bone and cartilage damage, when administered therapeutically in murine CIA and rat AA.
Negative_regulation (inhibitor) of JAK3 in cartilage associated with inflammation and arthritis
11) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374467 Disease Relevance 1.15 Pain Relevance 0.66
Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis

Introduction

Negative_regulation (inhibition) of Janus kinase 3 in Cartilage associated with rheumatoid arthritis
12) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Title Doc Link PMC2374467 Disease Relevance 0.71 Pain Relevance 0.27
These data support JAK3 inhibition as a new target for the treatment of RA.


Negative_regulation (inhibition) of JAK3 associated with rheumatoid arthritis
13) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374467 Disease Relevance 1.10 Pain Relevance 0.50
Hence, JAK3 inhibition provides a potentially beneficial target for the treatment of RA based upon its ability to inhibit multiple cytokines known to be involved in the pathogenesis of the disease.


Negative_regulation (inhibition) of JAK3 associated with rheumatoid arthritis, disease and cytokine
14) Confidence 0.32 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2374467 Disease Relevance 0.75 Pain Relevance 0.50
Therefore, inhibition of JAK3 has potential applications in the treatment of inflammation, allergy, autoimmune disorders, and organ transplant rejection [45].
Negative_regulation (inhibition) of JAK3 associated with autoimmune disease, inflammation, hypersensitivity and organ transplantation
15) Confidence 0.27 Published 2008 Journal Purinergic Signal Section Body Doc Link PMC2721774 Disease Relevance 0.67 Pain Relevance 0.16
A number of JAK3 inhibitors, such as WHI-P131, WHI-P154, and PNU156804, which are not highly selective against other members of the JAK family of kinases, have been reported and included in a review article [48].
Negative_regulation (inhibitors) of JAK3
16) Confidence 0.27 Published 2008 Journal Purinergic Signal Section Body Doc Link PMC2721774 Disease Relevance 0.66 Pain Relevance 0.15
PF-956980, a structurally close analog of CP-690550, has been reported to be a potent and selective inhibitor of JAK3 with IC50?
Negative_regulation (inhibitor) of JAK3
17) Confidence 0.27 Published 2008 Journal Purinergic Signal Section Body Doc Link PMC2721774 Disease Relevance 0.32 Pain Relevance 0.08
A number of JAK3 inhibitors have been disclosed in an abstract, manuscript, or at scientific meetings without disclosing their structure and/or pharmacology profile (for example, R348, an inhibitor of JAK3 and Syk [49]); such inhibitors are not covered in this review.
Negative_regulation (inhibitor) of JAK3
18) Confidence 0.27 Published 2008 Journal Purinergic Signal Section Body Doc Link PMC2721774 Disease Relevance 0.60 Pain Relevance 0.11
However, the reported and available JAK2 inhibitors have some degree of JAK3 inhibitory activity and therefore the observed effect could, at least partly, be due to concomitant JAK3 inhibition.
Negative_regulation (inhibition) of JAK3
19) Confidence 0.27 Published 2008 Journal Purinergic Signal Section Body Doc Link PMC2721774 Disease Relevance 0.55 Pain Relevance 0.11
In that regard, Kwak et al. [77] showed that AG-490, an inhibitor of Jak2/Jak3 activity, actually induced osteoclast survival by activating both the MEK/ERK and PI3K/PTEN/Akt cell survival pathway.
Negative_regulation (inhibitor) of Jak3 in osteoclast
20) Confidence 0.22 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.48 Pain Relevance 0.39

General Comments

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