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Drug-Target Interaction

Drug

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PubChem ID:60490
Structure:
Synonyms:
(+)-1-(1-benzo(b)thien-2-ylethyl)-1-hydroxyurea
(+-)-1-(1-Benzo(b)thien-2-ylethyl)-1-hydroxyurea
(+-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
(+/-)-1-(1-Benzo[b]thien-2-ylethyl)-1-hydroxyurea
1-[1-(1-benzothien-2-yl)ethyl]-1-hydroxyurea
1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea
111406-87-2
132880-11-6
133305-01-8
154003-29-9
A 64077
A-64077
Abbot 64077
Abbott 64077
Abbott brand of zileuton
ABBOTT-64077
ABT-077
AC-13198
AC1L1TCB
AKOS000280127
Ambap5426
Bio-0924
C063449
C11H12N2O2S
CCG-100901
CHEBI:10112
CHEMBL93
CPD000466377
CTI-02
D00414
DB00744
FT-0082368
HMS2051M20
HMS2089J12
HMS2093H06
HMS2235O04
Leutrol
LS-158908
MLS000759510
MLS001424079
N-(1-Benzo(b)thien-2-ylethyl)-N-hydroxyurea
N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxyurea
NCGC00159453-02
NCGC00159453-03
NCGC00159453-04
Prestwick0_001090
S1443_Selleck
SAM001246738
SMR000466377
UNII-V1L22WVE2S
Urea, N-(1-benzo(b)thien-2-ylethyl)-N-hydroxy-
urea, n-(1-benzo(b)thien-2-ylethyl)-n-hydroxy-, (+)-
Urea, N-(1-benzo(b)thien-2-ylethyl)-N-hydroxy-, (+-)-
ZILEUTON
Zileuton (USP/INN)
Zileuton [USAN:BAN:INN]
Zileuton [USAN:INN:BAN]
Zileuton-Supplied by Selleck Chemicals
Zileutonum
Zileutonum [INN-Latin]
Ziluton
Zyflo
Zyflo (TN)
Zyflo CR
Zyflo Filmtab
ZYFLO, Zileuton

Target

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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:

14570767
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor.. Ping Lu; Michael L Schrag; Donald E Slaughter; Conrad E Raab; Magang Shou; A David Rodrigues (2003) Drug metabolism and disposition: the biological fate of chemicals display abstract
Zileuton, a 5-lipoxygenase inhibitor, was evaluated as an inhibitor of cytochrome P450 activity in human liver microsomes. In the absence of preincubation, the racemate was found to be a weak inhibitor (IC50 > 100 microM) of phenacetin O-deethylation (POD) (CYP1A2), paclitaxel 6alpha-hydroxylation (CYP2C8), diclofenac 4'-hydroxylation (CYP2C9), (S)-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), testosterone 6beta-hydroxylation (CYP3A4), chlorzoxazone 6-hydroxylation (CYP2E1), and bupropion hydroxylation (CYP2B6). When preincubated with NADPH-fortified human liver microsomes in the absence of substrate, zileuton (racemate) was shown to inhibit POD. The effect was NADPH-, time-, and concentration-dependent, and was characterized by a kinact (maximal rate of enzyme inactivation) and apparent KI(inhibitor concentration that supports half the maximal rate of inactivation) of 0.035 min(-1) and 117 microM, respectively (kinact/KIratio of 0.0003 min-1 microM(-1)). Preincubation-dependent inhibition of POD activity was also observed with the individual (S)-(-)- and (R)-(+)-enantiomers of zileuton [(S)-(-)-zileuton; kinact, 0.037 min(-1), KI, 98.2 microM, kinact/KIratio, 0.0004 min(-1) microM(-1); (R)-(+)-zileuton; kinact, 0.012 min(-1), KI, 66.6 microM, kinact/KIratio, 0.0002 min(-1) microM(-1)]. In addition, the inhibition of CYP1A2 was not reversed in the presence of reduced glutathione, catalase, and superoxide dismutase and was refractory to dialysis. Therefore, zileuton was characterized as a mechanism-based inhibitor of human liver microsomal CYP1A2. Mechanism-based inhibition of CYP1A2 may explain why zileuton decreases the oral clearance of antipyrine, propranolol, (R)-warfarin, and theophylline, at doses that have a minimal effect on the pharmacokinetics of (S)-warfarin, phenytoin, and terfenadine.