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

Drug-Target Interaction

Drug

show drug details
PubChem ID:35703
Structure:
Synonyms:
2H-1-Benzopyran-2-one, 7-ethoxy-
31005-02-4
7-Ethoxy-1-benzopyran-2-one
7-ethoxy-2H-1-benzopyran-2-one
7-ethoxy-2H-chromen-2-one
7-ethoxychromen-2-one
7-Ethoxycoumarin
AC1L1U91
AKOS001042905
C017299
C11052
CHEBI:28184
CHEMBL191528
E-5002
E0538
E1379_SIGMA
EINECS 250-429-4
ETHOXYCOUMARIN
Ethylumbelliferone
herniarin
HMS1722P19
LS-193364
MolPort-001-759-189
ST50306946
ST5306946
STK371316
ZINC00057719

Target

show target details
Uniprot ID:NCPR_HUMAN
Synonyms:
CPR
NADPH--cytochrome P450 reductase
P450R
EC-Numbers:1.6.2.4
Organism:Homo sapiens
Human
PDB IDs:1B1C 3FJO
Structure:
3FJO

Binding Affinities:

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

References:

8694855
Requirements for cytochrome b5 in the oxidation of 7-ethoxycoumarin, chlorzoxazone, aniline, and N-nitrosodimethylamine by recombinant cytochrome P450 2E1 and by human liver microsomes.. H Yamazaki; M Nakano; E M Gillam; L C Bell; F P Guengerich; T Shimada (1996) Biochemical pharmacology display abstract
NADH-dependent 7-ethoxycoumarin O-deethylation activities could be reconstituted in systems containing cytochrome b5 (b5), NADH-b5 reductase, and bacterial recombinant P450 2E1 in 100 mM potassium phosphate buffer (pH 7.4) containing a synthetic phospholipid mixture and cholate. Replacement of NADH-b5 reductase with NADPH-P450 reductase yielded a 4-fold increase in 7-ethoxycoumarin O-deethylation activity, and further stimulation (approximately 1.5-fold) could be obtained when NADPH was used as an electron donor. Removal of b5 from the NADH- and NADPH-supported systems caused a 90% loss of 7-ethoxycoumarin O-deethylation activities in the presence of NADPH-P450 reductase, but resulted in complete loss of the activities in the absence of NADPH-P450 reductase. Km values were increased and Vmax values were decreased for 7-ethoxycoumarin O-deethylation when b5 was omitted from the NADPH-supported P450 2E1-reconstituted systems. Requirements for b5 in P450 2E1 systems were also observed in chlorzoxazone 6-hydroxylation, aniline p-hydroxylation, and N-nitrosodimethylamine N-demethylation. In human liver microsomes, NADH-dependent 7-ethoxycoumarin O-deethylation, chlorzoxazone 6-hydroxylation, aniline p-hydroxylation, and N-nitrosodimethylamine N-demethylation activities were found to be about 55, 41, 33, and 50%, respectively, of those catalyzed by NADPH-supported systems. Anti-rat NADPH-P450 reductase immunoglobulin G inhibited 7-ethoxycoumarin O-deethylation activity catalyzed by human liver microsomes more strongly in NADPH- than NADH-supported reactions, while anti-human b5 immunoglobulin G inhibited microsomal activities in both NADH- and NADPH-supported systems to similar extents. These results suggest that b5 is an essential component in P450 2E1-catalyzed oxidations of several substrates used, that about 10% of the activities occur via P450 2E1 reduction by NADPH-P450 reductase in the absence of b5, and that the NADH-supported system contributes, in part, to some reactions catalyzed by P450 2E1 in human liver microsomes.