INT98456

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Context Info
Confidence 0.42
First Reported 2001
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 17
Total Number 17
Disease Relevance 8.30
Pain Relevance 0.42

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

mitochondrion (Src) enzyme binding (Src) cytoplasm (Src)
cell proliferation (Src) cell adhesion (Src) nucleus (Src)
Anatomy Link Frequency
platelet 2
blood vessel 1
myeloid cells 1
Src (Mus musculus)
Pain Link Frequency Relevance Heat
Kinase C 4 98.94 Very High Very High Very High
Opioid 24 95.52 Very High Very High Very High
narcan 2 91.84 High High
substance P 2 67.20 Quite High
antagonist 16 64.80 Quite High
Potency 32 46.72 Quite Low
fortral 4 45.00 Quite Low
agonist 9 44.40 Quite Low
fibrosis 8 36.68 Quite Low
cytokine 13 33.92 Quite Low
Disease Link Frequency Relevance Heat
Cancer 216 99.28 Very High Very High Very High
Erythrocytosis 74 98.40 Very High Very High Very High
Philadelphia Chromosome 53 98.00 Very High Very High Very High
Reticulocytosis 10 97.72 Very High Very High Very High
Apoptosis 75 97.32 Very High Very High Very High
Blast Crisis 44 97.18 Very High Very High Very High
Myeloid Leukemia 448 96.80 Very High Very High Very High
Leukemia 83 96.68 Very High Very High Very High
Myelodysplastic Syndromes 185 93.20 High High
Adhesions 44 90.16 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Initial approval of dasatinib was based on data from the START (SRC/ABL Tyrosine kinase inhibition Activity: Research Trials of dasatinib) program, a series of multicenter, open-label phase 2 clinical trials in imatinib-resistant or -intolerant patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
Negative_regulation (inhibition) of SRC associated with leukemia, myeloid leukemia and philadelphia chromosome
1) Confidence 0.42 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2567340 Disease Relevance 0.96 Pain Relevance 0
CML: chronic myeloid leukemia; CP: chronic phase; AP: accelerated phase; BP: blast phase; TKI: tyrosine kinase inhibitor; IRIS: International Randomized Study of Interferon and STI571; CCyR: complete cytogenetic response; START: SRC/ABL Tyrosine kinase inhibition Activity: Research Trials of dasatinib; Ph+ ALL: Philadelphia chromosome-positive acute lymphoblastic leukemia; MCyR: major cytogenetic response; AE: adverse event; CHR: complete hematologic response.


Negative_regulation (inhibition) of SRC associated with leukemia, myeloid leukemia, philadelphia chromosome and blast crisis
2) Confidence 0.42 Published 2008 Journal J Hematol Oncol Section Body Doc Link PMC2567340 Disease Relevance 0.58 Pain Relevance 0
In complementary studies where diseased mice were treated with dasatinib, a potent inhibitor of both ABL and Src kinases, there was minimal response of polycythemia and reticulocytosis to a regimen that is very effective for treatment of mice inoculated with BCR-ABL-expressing cells [27].
Negative_regulation (inhibitor) of Src associated with reticulocytosis and erythrocytosis
3) Confidence 0.32 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.13 Pain Relevance 0
Like imatinib, nilotinib does not inhibit Src kinase and does not bind to the inactive conformation of Bcr-Abl.
Negative_regulation (inhibit) of Src
4) Confidence 0.23 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0 Pain Relevance 0
There is a possibility that one or more of the other six vertebrate Src family kinases might compensate for lack of these three, particularly Fyn, Yes, and c-Src, which are expressed in myeloid cells.
Negative_regulation (lack) of Src in myeloid cells
5) Confidence 0.21 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.77 Pain Relevance 0
Perhaps consistent with their ability to regulate blood vessel permeability, inhibition of FAK or Src signal transduction reduces tumor cell extravasation [43], [54].
Negative_regulation (inhibition) of Src in blood vessel associated with cancer
6) Confidence 0.19 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2680032 Disease Relevance 0.86 Pain Relevance 0
Dasatinib was initially developed as an inhibitor of the Src family of kinases such as Fyn, Yes, Src, and Lyk, but it also inhibits BCR-ABL, EphA2, platelet-derived growth factor receptor, and c-Kit.
Negative_regulation (inhibitor) of Src in platelet
7) Confidence 0.18 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697539 Disease Relevance 0.08 Pain Relevance 0
Dasatinib was initially developed as an inhibitor of the Src family of kinases such as Fyn, Yes, Src, and Lyk, but it also inhibits BCR-ABL, EphA2, platelet-derived growth factor receptor, and c-Kit.
Negative_regulation (inhibitor) of Src in platelet
8) Confidence 0.18 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697539 Disease Relevance 0.08 Pain Relevance 0
The disruption of the proto-oncogene Src is associated with the pathogenesis of human cancers.4 Several synthetic small molecule inhibitors of Src-family kinases (SFK) have been developed, such as PD180970, AP23464, CGP76030, dasatinib, and bosutinib.
Negative_regulation (inhibitors) of Src associated with cancer
9) Confidence 0.18 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886328 Disease Relevance 0.70 Pain Relevance 0
These include dasatinib (Sprycel®; BMS-354825, Bristol-Myers-Squibb), an orally bioavailable dual Bcr-Abl and Src inhibitor, and nilotinib (Tasigna®; AMN-107, Novartis), a potent selective Bcr-Abl inhibitor.
Negative_regulation (inhibitor) of Src
10) Confidence 0.17 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0.49 Pain Relevance 0
Dasatinib (BMS-354825) is a dual Src- and Abl-kinase inhibitor, 300-fold more potent Abl kinase inhibitor than imatinib, and FDA approved for CML (Lombardo et al 2004).
Negative_regulation (inhibitor) of Src associated with myeloid leukemia
11) Confidence 0.17 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721304 Disease Relevance 0.68 Pain Relevance 0
DSLET-mediated ERK activation was significantly inhibited by the Src kinase inhibitor, PP1 (10 ?
Negative_regulation (inhibitor) of Src
12) Confidence 0.15 Published 2002 Journal BMC Pharmacol Section Body Doc Link PMC88976 Disease Relevance 0 Pain Relevance 0.16
Reduced FAK, phospho-FAK, cSrc, phospho-Src, Arp2, F-actin, paxillin, phospho-paxillin protein levels after treatment with bicistronic constructs in 5310 cells further strengthened our hypothesis that our treatments inhibit the migratory potential of these xenografts.
Negative_regulation (Reduced) of Src
13) Confidence 0.14 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2904700 Disease Relevance 0.22 Pain Relevance 0
Based on the above, we postulate the following working model for anti-MCSP:TRAIL (see also Figure 6B); anti-MCSP:TRAIL binds to MCSP and inhibits MCSP-signaling, which includes inhibition of src-kinases and FAK, the STAT transcription factors, and various anti-apoptotic modulators such as p53, TOR, JNK.
Negative_regulation (inhibition) of src associated with apoptosis
14) Confidence 0.10 Published 2010 Journal Mol Cancer Section Body Doc Link PMC3000402 Disease Relevance 0.89 Pain Relevance 0
Other new agents are PKC 412 (inhibitor of protein kinase C, KIT, PDGFR, and VEGF), BMS-354825 (tyrosine kinase inhibitor of KIT, PDGFR, abl and src), oblimerson sodium (an antisense oligonucleotide inhibiting BCL-2), and CCI 779 (a rapamycin analogue inhibitor of the protein kinase mammalian target of rapamycin).
Negative_regulation (inhibitor) of src associated with kinase c
15) Confidence 0.08 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2503651 Disease Relevance 0.55 Pain Relevance 0.05
Two structurally distinct Src kinase inhibitors, 4-amino-5-(4-methylphenyl)7-(t-butyl)pyrazolo[3,4-d] pyrimidine (PP1) and a Src inhibitory peptide, increased the Ca(2+) currents, and no further increase in Ca(2+) currents was elicited by addition of naloxone and suramin.
Negative_regulation (inhibitors) of Src associated with narcan
16) Confidence 0.06 Published 2001 Journal J. Biol. Chem. Section Abstract Doc Link 11583988 Disease Relevance 0.18 Pain Relevance 0.21
Nascently phosphorylated CagA activates CSK and thereby leads to a subsequent inactivation of c-Src and Fyn [69].
Negative_regulation (inactivation) of Src
17) Confidence 0.02 Published 2008 Journal BMC Syst Biol Section Body Doc Link PMC2254585 Disease Relevance 0.14 Pain Relevance 0

General Comments

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