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Drug-Target Interaction

Drug

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PubChem ID:11963622
Structure:
Synonyms:
13755-38-9 (DIHYDRATE)
14402-89-2 (DISODIUM SALT)
15078-28-1
AIDS-085114
AIDS085114
CHEBI:7596
CID11963622
DB00325
Ferrate(2-), pentakis(cyano-.kappa.C)-nitrosyl
NCGC00166055-01
Nipride
Nipruss
Nitroferricyanide
Nitropress
Nitroprusside
pentacyanidonitrosylferrate(2-)
pentacyanidonitrosylferrate(III)
SNP
Sodium Nitroprusside
sodium nitroprusside extra pure
[Fe(CN)5(NO)](2-)
ATC-Codes:

Target

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Uniprot ID:CP1A1_HUMAN
Synonyms:
CYPIA1
Cytochrome P450 1A1
P450 form 6
P450-C
P450-P1
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

8170947
Inhibition of cytochromes P4501A by nitric oxide.. J Stadler; J Trockfeld; W A Schmalix; T Brill; J R Siewert; H Greim; J Doehmer (1994) Proceedings of the National Academy of Sciences of the United States of America display abstract
Inflammatory stimulation of the liver leads to the induction of nitric oxide (NO) biosynthesis. Because NO binds to the catalytic heme moiety of cytochromes P450 (CYPs), we investigated whether NO interferes with specific CYP-dependent metabolic pathways. In a first experimental approach V79 Chinese hamster cells genetically engineered for stable expression of rat and human CYP1A1 and -1A2 were used. Incubation with the NO donors sodium nitroprusside and S-nitrosylacetylpenicillamine led to a concentration-dependent inhibition of all four CYP enzymes. CYP1A1 was more sensitive to the inhibitory effect of NO than CYP1A2. In the second part of the study, endogenous NO synthesis was induced in rat hepatocytes by incubation with a mixture of cytokines and endotoxin. Concurrently, as NO production in hepatocytes increased within 24 hr, a decrease in CYP1A1-dependent benzo[a]pyrene turnover was observed to almost undetectable levels. The competitive inhibitor of NO synthesis, NG-monomethyl-L-arginine, was able to significantly restore CYP1A1 activity in the presence of cytokines and endotoxin. Inhibition of hepatocellular CYP activity by NO was predominantly due to a direct effect on the enzymes. However, NO-dependent inhibition of CYP expression at a transcriptional level was also demonstrated. Our results indicate that inhibition of NO biosynthesis in patients suffering from systemic inflammatory response syndromes may help to restore biotransformation capacity of the liver.