INT153410

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Context Info
Confidence 0.59
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 5
Total Number 12
Disease Relevance 10.71
Pain Relevance 3.98

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

cell differentiation (Jak2) cytosol (Jak2) signal transduction (Jak2)
histone binding (Jak2) cytoskeleton (Jak2) nucleus (Jak2)
Anatomy Link Frequency
blood 1
SNL 1
myeloid progenitor cell 1
red blood cell 1
Jak2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Potency 208 98.80 Very High Very High Very High
Spinal cord 5 98.80 Very High Very High Very High
Inflammation 168 98.70 Very High Very High Very High
allodynia 1 98.64 Very High Very High Very High
Arthritis 384 98.46 Very High Very High Very High
Thermal hyperalgesia 1 98.08 Very High Very High Very High
rheumatoid arthritis 176 97.42 Very High Very High Very High
psoriasis 24 97.04 Very High Very High Very High
intrathecal 1 94.28 High High
cytokine 235 89.68 High High
Disease Link Frequency Relevance Heat
Myeloproliferative Disorder 2 99.96 Very High Very High Very High
Hematological Disease 35 99.82 Very High Very High Very High
Myelofibrosis 23 99.40 Very High Very High Very High
Disease 86 99.04 Very High Very High Very High
Reprotox - General 1 8 98.80 Very High Very High Very High
INFLAMMATION 160 98.70 Very High Very High Very High
Neuropathic Pain 3 98.64 Very High Very High Very High
Arthritis 416 98.46 Very High Very High Very High
Anaemia 4 98.36 Very High Very High Very High
Hyperalgesia 1 98.08 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Over a dozen JAK2 inhibitors are in development, with the leading compounds such as INCB018424, TG101348 and others showing promising early results particularly for control of disease associated splenomegaly and symptoms.
Negative_regulation (inhibitors) of JAK2 associated with splenomegaly and disease
1) Confidence 0.59 Published 2009 Journal Expert Opin Emerg Drugs Section Abstract Doc Link 19552608 Disease Relevance 1.67 Pain Relevance 0.09
The two most likely mechanistic hypotheses which could explain observed clinical reductions in PBNC in RA subjects by CP-690,550 are: 1) suppression of bone marrow myeloid progenitor cell differentiation via a loss of selectivity and inhibition of JAK2; and 2) suppression of chemotactic and hematopoietic growth factors as an extension of the anti-inflammatory activity of CP-690,550.
Negative_regulation (inhibition) of JAK2 in myeloid progenitor cell associated with inflammation and rheumatoid arthritis
2) Confidence 0.47 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.24 Pain Relevance 0.18
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 JAK2 in blood
3) Confidence 0.47 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.77 Pain Relevance 0.20
New medical therapies for MF revolve around three main themes: immunomodulation (to assist anemia), hypomethylation strategies, and (the most robust pipeline) the use of targeted JAK2 inhibitors.
Negative_regulation (inhibitors) of JAK2 associated with anaemia and myelofibrosis
4) Confidence 0.43 Published 2010 Journal Curr Hematol Malig Rep Section Abstract Doc Link 20425392 Disease Relevance 1.74 Pain Relevance 0.09
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 JAK2 associated with hematological disease, inflammation, arthritis and potency
5) Confidence 0.35 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 1.07 Pain Relevance 0.62
First, reductions in PBNC were not observed non-clinically (in rodents (data not shown) and non-human primates [21] for up to 6 and 9 months of treatment, respectively; although a slight reduction in red blood cell parameters was observed in both species at dose levels where inhibition of JAK2 would be expected (data not shown)) or clinically in healthy volunteers, psoriasis and allograft patients (for up to 14 and 28 days of treatment, respectively) [9,10,21].
Negative_regulation (inhibition) of JAK2 in red blood cell associated with psoriasis
6) Confidence 0.35 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.42 Pain Relevance 0.21
Furthermore, we did not observe any inhibitory effects on erythropoiesis in the rat (normal or AIA) over the course of CP-690,550 treatment, which would have been expected if JAK2 was inhibited [14,16].
Negative_regulation (inhibited) of JAK2 associated with arthritis
7) Confidence 0.35 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.44 Pain Relevance 0.32
Decreases in PBNC following CP-690,550 treatment may thus be related to attenuation of inflammation and are likely not due to suppression of granulopoiesis through JAK2 inhibition.



Negative_regulation (inhibition) of JAK2 associated with inflammation
8) Confidence 0.35 Published 2010 Journal J Inflamm (Lond) Section Abstract Doc Link PMC2928212 Disease Relevance 0.76 Pain Relevance 0.39
However, it is recognized that this compound may have additional pharmacological effects on either granulopoiesis and/or PBNC at exaggerated clinical dose levels where loss of selectivity and cross-inhibition of JAK2 may occur.
Negative_regulation (inhibition) of JAK2
9) Confidence 0.35 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.73 Pain Relevance 0.31
Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt.
Negative_regulation (inhibitors) of JAK2 associated with myeloproliferative disorder and disease
10) Confidence 0.35 Published 2010 Journal Eur. J. Haematol. Section Title Doc Link 20528907 Disease Relevance 2.10 Pain Relevance 0.24
Additionally, the inhibitor demonstrated reduced potency against IL-6 activation of STAT3 and significantly reduced inhibition of JAK2-mediated GM-CSF signaling.
Negative_regulation (inhibition) of JAK2 associated with reprotox - general 1 and potency
11) Confidence 0.34 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2928212 Disease Relevance 0.10 Pain Relevance 0.43
STAT3 pathway blockade with Janus kinase 2 inhibitor AG490 attenuated both mechanical allodynia and thermal hyperalgesia in SNL rats.
Negative_regulation (inhibitor) of Janus kinase 2 in SNL associated with allodynia and thermal hyperalgesia
12) Confidence 0.27 Published 2008 Journal J. Neurochem. Section Abstract Doc Link 18636982 Disease Relevance 0.67 Pain Relevance 0.90

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