INT114718

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Context Info
Confidence 0.49
First Reported 2004
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 17
Total Number 21
Disease Relevance 4.69
Pain Relevance 4.69

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

small molecule metabolic process (CYP3A4) oxidoreductase activity (CYP3A4) endoplasmic reticulum (CYP3A4)
enzyme binding (CYP3A4) lipid metabolic process (CYP3A4) cytoplasm (CYP3A4)
Anatomy Link Frequency
body 8
liver 6
gut 3
intestine 3
CYP3A4 (Homo sapiens)
Pain Link Frequency Relevance Heat
Buprenorphine 19 98.72 Very High Very High Very High
methadone 35 98.08 Very High Very High Very High
Inflammation 119 95.44 Very High Very High Very High
Bioavailability 44 89.96 High High
Morphine 1 79.28 Quite High
noradrenaline 100 74.92 Quite High
Serotonin 145 74.20 Quite High
Potency 39 72.92 Quite High
Inflammatory stimuli 7 65.20 Quite High
agonist 79 62.12 Quite High
Disease Link Frequency Relevance Heat
Cancer 204 100.00 Very High Very High Very High
Rickets 56 99.80 Very High Very High Very High
Endometriosis (extended) 24 98.62 Very High Very High Very High
Inflammatory Bowel Disease 224 96.20 Very High Very High Very High
Osteogenic Sarcomas 38 89.24 High High
Apoptosis 47 86.72 High High
INFLAMMATION 84 86.56 High High
Infection 39 85.20 High High
Breast Cancer 84 84.56 Quite High
Lung Cancer 16 81.68 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The metabolism of BUP was examined using human liver microsomes (HLM) and Ad293 P450-transfected cell lines, as well as CYP 3A4 and 2C8 recombinant isoforms.
Spec (examined) Positive_regulation (transfected) of Spec (examined) Gene_expression (transfected) of CYP 3A4 in liver associated with buprenorphine
1) Confidence 0.49 Published 2005 Journal Drug Metab. Dispos. Section Abstract Doc Link 15743975 Disease Relevance 0 Pain Relevance 1.17
In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4.
Neg (not) Positive_regulation (stereoselective) of Neg (not) Gene_expression (stereoselective) of CYP3A4
2) Confidence 0.47 Published 2007 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 17259447 Disease Relevance 0 Pain Relevance 1.12
In human liver microsomes with high and low CYP2B6 expression but equivalent CYP3A4 expression, high CYP2B6 expression microsomes generated twice the amount of EDDP from 10 microg/ml of methadone than low CYP2B6 expression microsomes.
Positive_regulation (equivalent) of Gene_expression (expression) of CYP3A4 in liver associated with methadone
3) Confidence 0.46 Published 2004 Journal Chirality Section Abstract Doc Link 14628297 Disease Relevance 0 Pain Relevance 1.16
Therefore, an expected variability in CYP3A4 gene expression among different populations should be considered (Hustert et al. 2001; Koch et al. 2002; Lin et al. 2002).
Positive_regulation (variability) of Gene_expression (expression) of CYP3A4
4) Confidence 0.46 Published 2006 Journal Biomark Insights Section Body Doc Link PMC2716776 Disease Relevance 0.13 Pain Relevance 0
The drug is widely distributed in the body, with low protein binding and a high volume of distribution (see Table 2).118,119 Following oral absorption, venlafaxine undergoes extensive first-pass hepatic metabolism, where conversion to the active metabolite, desvenlafaxine, occurs via demethylation.157 This reaction is mediated by CYP2D6.120 Desvenlafaxine is further metabolized by CYP3A4.122 Other metabolic pathways for venlafaxine include N-demethylation which is probably mediated by CYP3A4.157 CYP2C9 and CYP2C19 isoenzymes may also be involved in the metabolic pathways of both drugs.121
Positive_regulation (by) of Gene_expression (isoenzymes) of CYP3A4 in body
5) Confidence 0.44 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0.18
The drug is widely distributed in the body, with low protein binding and a high volume of distribution (see Table 2).118,119 Following oral absorption, venlafaxine undergoes extensive first-pass hepatic metabolism, where conversion to the active metabolite, desvenlafaxine, occurs via demethylation.157 This reaction is mediated by CYP2D6.120 Desvenlafaxine is further metabolized by CYP3A4.122 Other metabolic pathways for venlafaxine include N-demethylation which is probably mediated by CYP3A4.157 CYP2C9 and CYP2C19 isoenzymes may also be involved in the metabolic pathways of both drugs.121
Positive_regulation (by) of Gene_expression (isoenzymes) of CYP3A4 in body
6) Confidence 0.44 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0.20
The drug is widely distributed in the body, with low protein binding and a high volume of distribution (see Table 2).118,119 Following oral absorption, venlafaxine undergoes extensive first-pass hepatic metabolism, where conversion to the active metabolite, desvenlafaxine, occurs via demethylation.157 This reaction is mediated by CYP2D6.120 Desvenlafaxine is further metabolized by CYP3A4.122 Other metabolic pathways for venlafaxine include N-demethylation which is probably mediated by CYP3A4.157 CYP2C9 and CYP2C19 isoenzymes may also be involved in the metabolic pathways of both drugs.121
Positive_regulation (by) of Gene_expression (metabolized) of CYP3A4 in body
7) Confidence 0.39 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0.20
The drug is widely distributed in the body, with low protein binding and a high volume of distribution (see Table 2).118,119 Following oral absorption, venlafaxine undergoes extensive first-pass hepatic metabolism, where conversion to the active metabolite, desvenlafaxine, occurs via demethylation.157 This reaction is mediated by CYP2D6.120 Desvenlafaxine is further metabolized by CYP3A4.122 Other metabolic pathways for venlafaxine include N-demethylation which is probably mediated by CYP3A4.157 CYP2C9 and CYP2C19 isoenzymes may also be involved in the metabolic pathways of both drugs.121
Positive_regulation (by) of Gene_expression (metabolized) of CYP3A4 in body
8) Confidence 0.39 Published 2010 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2938284 Disease Relevance 0 Pain Relevance 0.20
Activation of this pathway leads to enhanced expression of cytochrome CYP3A4 in both tumor cell lines and in mice which enhances metabolic degradation of drugs thus resulting in drug resistance (Mani et al 2005).
Positive_regulation (enhanced) of Gene_expression (expression) of CYP3A4 associated with cancer
9) Confidence 0.36 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727900 Disease Relevance 0.39 Pain Relevance 0
Activation of this pathway leads to enhanced expression of cytochrome CYP3A4 in both tumor cell lines and in mice which enhances metabolic degradation of drugs thus resulting in drug resistance (Mani et al 2005).
Positive_regulation (leads) of Gene_expression (expression) of CYP3A4 associated with cancer
10) Confidence 0.36 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727900 Disease Relevance 0.39 Pain Relevance 0
Activation of this pathway leads to enhanced expression of cytochrome CYP3A4 in both tumor cell lines and in mice which enhances metabolic degradation of drugs thus resulting in drug resistance (Mani et al 2005).
Positive_regulation (enhances) of Gene_expression (expression) of CYP3A4 associated with cancer
11) Confidence 0.36 Published 2008 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2727900 Disease Relevance 0.38 Pain Relevance 0
It has been observed that decreased content of CYP3A4 was not associated with increased CYP3A4 mRNA, probably indicating the absence of a feedback mechanism for CYP3A4 expression.
Positive_regulation (mechanism) of Gene_expression (expression) of CYP3A4
12) Confidence 0.33 Published 2007 Journal Nutr J Section Body Doc Link PMC2147024 Disease Relevance 0 Pain Relevance 0.04
The 2677G > T polymorphism has recently been suggested as the possible candidate.38 Persons homozygous for the MDR1 2677T allele, which is frequently linked to the 3435T allele, show enhanced constitutive CYP3A4 expression in the liver and gut when compared to subjects homozygous for the 2677G allele.39
Positive_regulation (enhanced) of Gene_expression (expression) of CYP3A4 in gut
13) Confidence 0.25 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697529 Disease Relevance 0.26 Pain Relevance 0
It upregulates CYP3A4 expression, while repressing CYP24 and CYP2D25 expression in the liver and intestine.


Positive_regulation (upregulates) of Gene_expression (expression) of CYP3A4 in intestine
14) Confidence 0.23 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.67 Pain Relevance 0.15
In contrast, the variants A370T and V140M show 1.5-2 fold enhancement in the basal expression of a CYP3A4 promoter reporter gene, but lack any significant effect on transcriptional activation.
Positive_regulation (enhancement) of Gene_expression (expression) of CYP3A4
15) Confidence 0.23 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0 Pain Relevance 0
Similarly, activation of SXR in endometrial cancer cell lines by many endocrine-disrupting chemicals has been shown to induce CYP3A4/CYP3A7 expression [Masuyama et al., 2003].
Positive_regulation (induce) of Gene_expression (expression) of CYP3A4 associated with endometriosis (extended)
16) Confidence 0.17 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.70 Pain Relevance 0.06
Single nucleotide polymorphisms (SNPs) in SXR should be a major contributor to CYP3A4 expression and activity.
Positive_regulation (contributor) of Gene_expression (expression) of CYP3A4
17) Confidence 0.17 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.22 Pain Relevance 0
Thus, SXR downregulation would reduce expression of CYP3A4, thereby increasing local estrogen levels and/or increasing sensitivity of estrogen receptor to estradiol [Cheng et al., 2001].
Positive_regulation (increasing) of Gene_expression (expression) of CYP3A4
18) Confidence 0.15 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.43 Pain Relevance 0
These results are consistent with the possibility that SNPs in SXR can contribute to the inter-individual variability of CYP3A4 expression and drug response.
Positive_regulation (contribute) of Gene_expression (expression) of CYP3A4
19) Confidence 0.15 Published 2009 Journal Nuclear Receptor Signaling Section Body Doc Link PMC2646121 Disease Relevance 0.19 Pain Relevance 0.05
The 2677G > T polymorphism has recently been suggested as the possible candidate.38 Persons homozygous for the MDR1 2677T allele, which is frequently linked to the 3435T allele, show enhanced constitutive CYP3A4 expression in the liver and gut when compared to subjects homozygous for the 2677G allele.39
Positive_regulation (enhanced) of in liver Gene_expression (expression) of CYP3A4 in gut
20) Confidence 0.08 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697529 Disease Relevance 0.26 Pain Relevance 0

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