INT3623

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Context Info
Confidence 0.55
First Reported 1976
Last Reported 2010
Negated 0
Speculated 0
Reported most in Abstract
Documents 49
Total Number 49
Disease Relevance 27.39
Pain Relevance 13.52

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

peptidase activity (CTSB) mitochondrion (CTSB) extracellular space (CTSB)
extracellular region (CTSB) intracellular (CTSB) lysosome (CTSB)
Anatomy Link Frequency
plasma 4
brain 2
HeLa 2
Notch 1
cleavage 1
CTSB (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 98 99.92 Very High Very High Very High
Abeta 138 99.64 Very High Very High Very High
bradykinin 225 99.24 Very High Very High Very High
Inflammation 91 97.64 Very High Very High Very High
Eae 28 95.64 Very High Very High Very High
diclofenac 3 93.04 High High
Spinal cord 3 91.28 High High
Hippocampus 8 88.44 High High
cytokine 48 88.40 High High
Dopamine 1 88.40 High High
Disease Link Frequency Relevance Heat
Coagulation Disorder 3 100.00 Very High Very High Very High
Disease 718 99.96 Very High Very High Very High
Toxicity 28 99.58 Very High Very High Very High
Congenital Anomalies 10 99.56 Very High Very High Very High
Alzheimer's Dementia 82 99.52 Very High Very High Very High
Targeted Disruption 101 99.18 Very High Very High Very High
Neurodegenerative Disease 14 98.28 Very High Very High Very High
Cognitive Disorder 16 98.16 Very High Very High Very High
Pancreatitis 23 98.08 Very High Very High Very High
Leukemia 4 97.94 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Inhibition of cathepsin B1 may be one way in which some of the drugs tested exercise their therapeutic effect in rheumatic diseases.
Negative_regulation (Inhibition) of cathepsin B1 associated with rheumatic diseases
1) Confidence 0.55 Published 1976 Journal Z Rheumatol Section Abstract Doc Link 817531 Disease Relevance 0.17 Pain Relevance 0.15
Salicylates, however, inhibited cathepsin B1 only at much higher concentrations (10(-2) M.
Negative_regulation (inhibited) of cathepsin B1
2) Confidence 0.55 Published 1976 Journal Z Rheumatol Section Abstract Doc Link 817531 Disease Relevance 0.08 Pain Relevance 0.16
The inhibitory effect on cathepsin B1 of 39 antirheumatic and other agents has been studied.
Negative_regulation (effect) of cathepsin B1
3) Confidence 0.40 Published 1976 Journal Z Rheumatol Section Abstract Doc Link 817531 Disease Relevance 0.06 Pain Relevance 0.11
Therapeutic potential of gamma-secretase inhibitors and modulators.
Negative_regulation (inhibitors) of gamma-secretase
4) Confidence 0.35 Published 2008 Journal Curr Top Med Chem Section Title Doc Link 18220933 Disease Relevance 0.82 Pain Relevance 0.35
According to the beta-amyloid (Abeta) hypothesis, compounds that inhibit gamma-secretase, the pivotal enzyme that generates Abeta, are potential therapeutics for Alzheimer's disease (AD).
Negative_regulation (inhibit) of gamma-secretase associated with alzheimer's dementia, disease and abeta
5) Confidence 0.35 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.67 Pain Relevance 0.17
Studies in both transgenic and non-transgenic animal models of AD have indicated that gamma-secretase inhibitors, administered by the oral route, are able to lower brain Abeta concentrations.
Negative_regulation (inhibitors) of gamma-secretase in brain associated with targeted disruption, disease and abeta
6) Confidence 0.35 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.73 Pain Relevance 0.24
Given the uncertain Abeta reduction target and the potential for mechanism-based toxicity, it has been suggested that biomarkers for efficacy (cerebrospinal fluid Abeta42 levels) and toxicity (plasma adipsin levels) would be helpful in initial clinical trials with gamma-secretase inhibitors.
Negative_regulation (inhibitors) of gamma-secretase in plasma associated with toxicity and abeta
7) Confidence 0.35 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.38 Pain Relevance 0.25
Gamma-secretase inhibitors may cause abnormalities in the gastrointestinal tract, thymus and spleen in rodents.
Negative_regulation (inhibitors) of Gamma-secretase in spleen associated with congenital anomalies
8) Confidence 0.35 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.84 Pain Relevance 0.38
The resulting impaired cathepsin B mediated trypsinogen activation seems not be a pancreatitis promoting pathogenic step.


Negative_regulation (impaired) of cathepsin B associated with pancreatitis
9) Confidence 0.28 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.47 Pain Relevance 0
Moreover, inhibition of cathepsin B reduces Abeta peptide levels in brain.
Negative_regulation (inhibition) of cathepsin B in brain associated with abeta
10) Confidence 0.22 Published 2006 Journal BioDrugs Section Abstract Doc Link 16626168 Disease Relevance 0.74 Pain Relevance 0.30
At inhibitory concentrations, on the other hand, biochemical readouts reminiscent of a nonselective gamma-secretase inhibition were obtained.
Negative_regulation (inhibition) of gamma-secretase
11) Confidence 0.19 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15304503 Disease Relevance 0.40 Pain Relevance 0.46
Because Abeta peptides are thought to be causative for Alzheimer's disease, inhibiting gamma-secretase represents a potential treatment for this neurodegenerative condition.
Negative_regulation (inhibiting) of gamma-secretase associated with neurodegenerative disease, disease and abeta
12) Confidence 0.19 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15304503 Disease Relevance 0.55 Pain Relevance 0.35
In addition to the anti-inflammatory effects of NSAIDs to block cylooxygenase, it has been shown recently that a subset of NSAIDs selectively inhibits the secretion of highly amyloidogenic Abeta42 from cultured cells, although the molecular target(s) of NSAIDs in reducing the activity of gamma-secretase for Abeta42 generation (gamma(42)-secretase) still remain unknown.
Negative_regulation (reducing) of secretase associated with inflammation and cinod
13) Confidence 0.18 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.34 Pain Relevance 0.55
Our data suggest that SSide is a direct inhibitor of gamma-secretase that preferentially affects the gamma(42)-secretase activity.
Negative_regulation (inhibitor) of secretase
14) Confidence 0.18 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.26 Pain Relevance 0.38
Here we show that sulindac sulfide (SSide) directly acts on gamma-secretase and preferentially inhibits the gamma(42)-secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitro gamma-secretase assay using recombinant amyloid beta precursor protein C100 as a substrate.
Negative_regulation (inhibits) of secretase in HeLa associated with alzheimer's dementia
15) Confidence 0.18 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.33 Pain Relevance 0.50
Inhibition of gamma-secretase has been shown to reduce Abeta production.
Negative_regulation (Inhibition) of gamma-secretase associated with abeta
16) Confidence 0.15 Published 2006 Journal Drugs Section Abstract Doc Link 17112302 Disease Relevance 0.70 Pain Relevance 0.26
Involvement of gamma-secretase in cell differentiation may preclude complete blockade of gamma-secretase for prolonged times in vivo.
Negative_regulation (blockade) of gamma-secretase
17) Confidence 0.15 Published 2006 Journal Drugs Section Abstract Doc Link 17112302 Disease Relevance 0.66 Pain Relevance 0.33
Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation.
Negative_regulation (inhibitor) of secretase associated with abeta
18) Confidence 0.13 Published 2003 Journal J. Biol. Chem. Section Title Doc Link 12637581 Disease Relevance 0.35 Pain Relevance 0.56
Here we show that sulindac sulfide (SSide) directly acts on gamma-secretase and preferentially inhibits the gamma(42)-secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitro gamma-secretase assay using recombinant amyloid beta precursor protein C100 as a substrate.
Negative_regulation (inhibits) of secretase in HeLa associated with alzheimer's dementia
19) Confidence 0.13 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.34 Pain Relevance 0.50
Gamma-secretase inhibitors may cause abnormalities in the gastrointestinal tract, thymus and spleen in rodents.
Negative_regulation (inhibitors) of Gamma-secretase in thymus associated with congenital anomalies
20) Confidence 0.12 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.84 Pain Relevance 0.38

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