Home
Drugs
Targets
Pathways
Ontologies
Cyp450s
Adv.search
Help/FAQ

Drug-Target Interaction

Drug

show drug details
PubChem ID:47318
Structure:
Synonyms:
35 972 R.P.
3H-1,2-DITHIOLE-3-THIONE, 4-METHYL-5-PYRAZINYL-
4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione
4-Methyl-5-(pyrazinyl)-3H-1,2-dithiole-3-thione
4-methyl-5-pyrazin-2-yl-3H-1,2-dithiole-3-thione
4-methyl-5-pyrazin-2-yldithiole-3-thione
4-Methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione
4-methyl-PDT
5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione
5-(2-Pyrazinyl)-4-methyl-1,2-dithiole-3-thione
64224-21-1
AB1004854
AC1L2HUC
AIDS-042741
AIDS042741
BRN 0978110
C026209
C8H6N2S3
CCRIS 4048
CCRIS 4048;
CHEMBL178459
CID47318
EINECS 264-736-6
HMS2090F09
LS-7628
NCI60_003092
NSC 347901
NSC347901
OLT
Oltipraz
Oltipraz [INN]
Oltiprazum
Oltiprazum [INN-Latin]
RP 35972
RP-35,972
RP-35972
UNII-6N510JUL1Y

Target

show target details
Uniprot ID:CP1A2_HUMAN
Synonyms:
CYPIA2
Cytochrome P450 1A2
P(3)450
P450 4
P450-P3
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:2HI4
Structure:
2HI4

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

7585637
Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture.. S LangouŰt; B Coles; F Morel; L Becquemont; P Beaune; F P Guengerich; B Ketterer; A Guillouzo (1995) Cancer research display abstract
Dithiolethiones are thought to act as potent chemoprotective agents against aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rat by inducing glutathione S-transferases (GSTs). To determine whether these antioxidants can be similarly effective in human beings, we have investigated metabolism of AFB1, in primary human hepatocytes with or without pretreatment by oltipraz (OPZ), a synthetic derivative of the natural 1,2-dithiole-3-thione. Aflatoxin M1 (AFM1), glutathione conjugates of AFB1 oxides (AFBSGs), and unchanged AFB1 were quantitated in cultures derived from eight human liver donors. Parenchymal cells obtained from the three GST M1-positive livers metabolized AFB1 to AFM1 and to AFBSGs derived from the isomeric exo-and endo-8,9-oxides, whereas no AFBSGs were formed in the GST M1-null cells. Pretreatment of the cells with 3-methylcholanthrene or rifampicin, inducers of CYP1A2 and CYP3A4, respectively, caused a significant increase in AFB1 metabolism. Although OPZ induced GST A2, and to a lesser extent GST A1 and GST M1, it decreased formation of AFM1 and AFBSG, which involves CYP1A2 and CYP3A4. Inhibition by OPZ of AFB1 metabolism by reducing CYP1A2 and CYP3A4 was also demonstrated by decreased activity of their monooxygenase activities toward ethoxyresorufin and nifedipine, respectively. The significant inhibition by OPZ of human recombinant yeast CYP1A2 and CYP3A4 was also shown. These results demonstrate that AFBSG can be formed by GST M1-positive human hepatocytes only, and suggest that chemoprotection with OPZ is due to an inhibition of activation of AFB1, in addition to a GST-dependent inactivation of the carcinogenic exo-epoxide.