INT328808

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Context Info
Confidence 0.42
First Reported 2010
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 9
Disease Relevance 7.01
Pain Relevance 3.64

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

nucleus (Jak1) cytoplasm (Jak1)
Anatomy Link Frequency
blood 2
Jak1 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Inflammation 189 99.34 Very High Very High Very High
Arthritis 432 99.28 Very High Very High Very High
rheumatoid arthritis 198 98.72 Very High Very High Very High
Potency 234 98.24 Very High Very High Very High
cytokine 261 97.76 Very High Very High Very High
psoriasis 27 81.60 Quite High
anesthesia 9 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
INFLAMMATION 180 99.34 Very High Very High Very High
Arthritis 468 99.28 Very High Very High Very High
Hematological Disease 36 98.92 Very High Very High Very High
Rheumatoid Arthritis 198 98.72 Very High Very High Very High
Disease 90 95.52 Very High Very High Very High
Immunization 81 89.44 High High
Pressure And Volume Under Development 27 85.12 High High
Psoriasis 27 81.60 Quite High
Neutropenia 9 50.40 Quite High
Autoimmune Disease 9 46.64 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
, as inhibition of JAK1 could be sufficient.
Negative_regulation (inhibition) of JAK1
1) Confidence 0.42 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.16 Pain Relevance 0.15
Results from this study demonstrate a strong PK/PD relationship between inhibition of JAK1 and JAK3, efficacy, and the inhibition of inflammatory cytokines and neutrophilia in the rat AIA model with CP-690,550 (Tables 1 and 2, Figures 1 and 2).
Negative_regulation (inhibition) of JAK1 associated with inflammation, arthritis and cytokine
2) Confidence 0.42 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 1.26 Pain Relevance 0.62
Therefore, exposures of CP-690,550 which are associated with efficacy and PBNC reductions in human RA patients and in the rat AIA model correlate primarily with the inhibition of JAK1 and JAK3 and not that of JAK2, based on the assay results in Table 1.


Negative_regulation (inhibition) of JAK1 associated with rheumatoid arthritis and arthritis
3) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.37 Pain Relevance 0.23
Results from this investigation suggest that CP-690,550 is a potent inhibitor of JAK1 and JAK3 with potentially reduced cellular potency for JAK2.
Negative_regulation (inhibitor) of JAK1 associated with potency
4) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Abstract Doc Link PMC2928212 Disease Relevance 1.04 Pain Relevance 0.58
The plasma concentration of CP-690,550 at efficacious doses was above the in vitro whole blood IC50 of JAK1 and JAK3 inhibition, but not that of JAK2.


Negative_regulation (inhibition) of JAK1 in blood
5) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Abstract Doc Link PMC2928212 Disease Relevance 1.04 Pain Relevance 0.58
The aim of the current study was to characterize the potency and selectivity of CP-690,550 for the JAK family members and to determine if PBNC reductions in the context of arthritis are related to the anti-inflammatory efficacy of CP-690,550 (through JAK 1 and JAK3 inhibition), or due to inhibition of hematopoiesis through inhibition of JAK2 at efficacious exposures.
Negative_regulation (inhibition) of JAK 1 associated with hematological disease, inflammation, arthritis and potency
6) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 1.12 Pain Relevance 0.64
Thirdly, in vitro human selectivity data suggests that clinically efficacious doses of CP-690,550 of up to 30 mg would inhibit the JAK1 and JAK3 enzymes, but not JAK2 (Tables 1 and 2).
Negative_regulation (inhibit) of JAK1
7) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.61 Pain Relevance 0.27
These data suggest the importance of JAK1 and JAK3 inhibition for efficacy, since ED50 exposures were below those needed for JAK2 inhibition in whole blood.
Negative_regulation (inhibition) of JAK1 in blood
8) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.82 Pain Relevance 0.23
Collectively, results from this investigation suggest that the reductions in PBNC in human RA patients may be an indirect consequence of the anti-inflammatory activity of CP-690,550 and/or the inhibition of JAK1 and JAK3 activity, but not JAK2.
Negative_regulation (inhibition) of JAK1 associated with inflammation and rheumatoid arthritis
9) Confidence 0.31 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.57 Pain Relevance 0.34

General Comments

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