INT149831

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Context Info
Confidence 0.52
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 8
Total Number 16
Disease Relevance 13.01
Pain Relevance 4.36

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

nucleus (Dmbx1) DNA binding (Dmbx1)
Anatomy Link Frequency
dorsal root 1
CPA 1
liver sinusoids 1
cardiovascular system 1
nerve 1
Dmbx1 (Mus musculus)
Pain Link Frequency Relevance Heat
Demyelination 115 99.46 Very High Very High Very High
agonist 135 99.44 Very High Very High Very High
Neuropathic pain 169 99.12 Very High Very High Very High
antagonist 135 99.08 Very High Very High Very High
Hyperalgesia 12 99.06 Very High Very High Very High
withdrawal 18 96.36 Very High Very High Very High
Spinal cord 94 94.44 High High
Thermal hyperalgesia 17 94.24 High High
allodynia 48 93.24 High High
alcohol 19 88.32 High High
Disease Link Frequency Relevance Heat
Demyelinating Disease 140 99.46 Very High Very High Very High
Cancer 220 99.36 Very High Very High Very High
Neuropathic Pain 219 99.12 Very High Very High Very High
Hyperalgesia 29 99.06 Very High Very High Very High
Metastasis 91 98.76 Very High Very High Very High
Skin Cancer 27 96.16 Very High Very High Very High
Breast Cancer 27 95.52 Very High Very High Very High
Nervous System Injury 90 95.32 Very High Very High Very High
Targeted Disruption 140 91.72 High High
Ovarian Cancer 152 86.72 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This decline may be caused by the product-inhibition of ATX, since ATX activity is inhibited by high levels of LPA [40].
Negative_regulation (inhibited) of ATX
1) Confidence 0.52 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.24 Pain Relevance 0.12
This decline may be caused by the product-inhibition of ATX, since ATX activity is inhibited by high levels of LPA [40].
Negative_regulation (inhibition) of ATX
2) Confidence 0.52 Published 2009 Journal Mol Pain Section Body Doc Link PMC2780384 Disease Relevance 0.24 Pain Relevance 0.12
Therefore, targeted inhibition of ATX-mediated LPA biosynthesis as well as LPA1 receptor and its downstream pathways may represent a novel way to prevent nerve injury-induced neuropathic pain.



Negative_regulation (inhibition) of ATX in nerve associated with nervous system injury and neuropathic pain
3) Confidence 0.40 Published 2008 Journal Mol Pain Section Body Doc Link PMC2277392 Disease Relevance 1.08 Pain Relevance 0.71
The hyperalgesia was completely abolished in lpa1-/- mice, and reduced by 50% in atx+/- mice.
Negative_regulation (reduced) of atx associated with hyperalgesia
4) Confidence 0.35 Published 2008 Journal Mol Pain Section Abstract Doc Link PMC2277392 Disease Relevance 1.21 Pain Relevance 0.71
The reason LPC did not cause demyelination, may be attributed to the loss of ATX throughout the isolation and preparation processes of dorsal root fibers in the ex vivo study, consistent with LPA production [29,35].
Negative_regulation (loss) of ATX in dorsal root associated with demyelination
5) Confidence 0.32 Published 2010 Journal Mol Pain Section Body Doc Link PMC2989310 Disease Relevance 1.19 Pain Relevance 0.64
Accordingly, pharmacological inhibition of ATX may be a viable and potentially effective way to interfere with LPA signaling in the cardiovascular system and possibly other settings such as tumor metastasis for therapeutic benefit.
Negative_regulation (inhibition) of ATX in cardiovascular system associated with metastasis
6) Confidence 0.29 Published 2008 Journal Curr Drug Targets Section Abstract Doc Link 18691016 Disease Relevance 0.89 Pain Relevance 0.10
Furthermore, the LPC-induced response was also significantly, but partially reduced in heterozygous mutant mice for the ATX gene.
Negative_regulation (reduced) of ATX
7) Confidence 0.22 Published 2008 Journal Neuroscience Section Abstract Doc Link 18280050 Disease Relevance 0.86 Pain Relevance 0.93
However, inhibition of ATX does not lead to an anti-tumour effect, as cancer cells continue to proliferate although their metastasis is reduced.
Negative_regulation (inhibition) of ATX associated with cancer and metastasis
8) Confidence 0.11 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.03 Pain Relevance 0.04
CPA and its synthetic 3CCPA analogues inhibit cancer metastasis through an as yet unidentified mechanism, which includes the inhibition of ATX (Baker et al., 2006; Uchiyama et al., 2007; Fujiwara, 2008).
Negative_regulation (inhibition) of ATX in CPA associated with cancer and metastasis
9) Confidence 0.11 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 0.20 Pain Relevance 0.24
Hence, selective agonists of this receptor subtype that inhibit ATX might prove to be useful in limiting cancer invasion and metastasis (Baker et al., 2006; Williams et al., 2009).
Negative_regulation (inhibit) of ATX associated with cancer, agonist and metastasis
10) Confidence 0.11 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.41 Pain Relevance 0.13
Pure ATX inhibitors also face another challenge; intravenously injected recombinant ATX is very rapidly >10-min cleared within the liver sinusoids (Jansen et al., 2009).
Negative_regulation (inhibitors) of ATX in liver sinusoids
11) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.00 Pain Relevance 0.12
Hence, the challenge now is to combine receptor antagonism with the inhibition of ATX to obtain anti-tumour and anti-metastatic drug candidates.
Negative_regulation (inhibition) of ATX associated with cancer
12) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.02 Pain Relevance 0.11
However, its synthetic hydrolysis-resistant 3-carba analogue (3CCPA 18:1) is a selective weak agonist of LPA5/GPR92 that fails to activate LPA1/2/3/4 and also inhibits ATX (Baker et al., 2006; Fujiwara, 2008).
Negative_regulation (inhibits) of ATX associated with agonist
13) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 0.19 Pain Relevance 0.19
(Zhang et al., 2009a) have developed alpha-bromophosphonate analogues of LPA that inhibit ATX activity and also are antagonists of LPA1,2,3,4,5 GPCR and showed that these dual-action compounds not only reduce breast cancer metastasis but also inhibit tumour growth.
Negative_regulation (inhibit) of ATX associated with cancer, antagonist, breast cancer and metastasis
14) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 0.96 Pain Relevance 0.08
Another new direction is to explore agonists of LPA4 and LPA5 that also inhibit ATX.
Negative_regulation (inhibit) of ATX associated with agonist
15) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 1.24 Pain Relevance 0.13
ATX is a member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family and is also known as NPP2.
Negative_regulation (known) of ATX
16) Confidence 0.08 Published 2010 Journal British Journal of Pharmacology Section Body Doc Link PMC2989581 Disease Relevance 0.25 Pain Relevance 0

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