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Drug-Target Interaction

Drug

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PubChem ID:456201
Structure:
Synonyms:
()-ketoconazole
(+)-Ketoconazole
(+-)-cis-1-Acetyl-4-(p-((2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazine
(+/-)-cis-1-Acetyl-4-(4-[(2-[2,4-dichlorophenyl]-2-[1H-imidazol-1-ylmethyl]-1,3-dioxolan-4-yl)-methoxy]phenyl)piperazine
(2R,4S)-ketoconazole
1-acetyl-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-
1-acetyl-4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine
65277-42-1
79156-75-5
AIDS-007337
AIDS-112210
AIDS007337
AIDS112210
Ambap5952
BIM-0050645.0001
BPBio1_000635
BRN 4303081
BSPBio_000577
C26H28Cl2N4O4
CHEBI:48336
CIS-1-ACETYL-4-(4-((2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)PIPERAZINE
cis-1-Acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine
CPD000058460
EINECS 265-667-4
EU-0100666
Extina
Fungarest
Fungoral
HSDB 7447
K1003_SIGMA
KET
Ketoconazol
Ketoconazol [INN-Spanish]
Ketoconazole
Ketoconazole [USAN:INN:BAN:JAN]
Ketoconazolum
Ketoconazolum [INN-Latin]
Ketoderm
Ketoisdin
KT
KTN
KW-1414
KZ
Lopac0_000666
LS-110149
MLS000069784
MLS000758224
MLS001146934
NCGC00025000-01
NCGC00025000-02
NCGC00025000-03
NCGC00025000-04
NCGC00025000-05
NCGC00025000-06
NCGC00025000-07
Nizoral
NIZORAL A-D
NSC 317629
NSC317629
Orifungal M
Panfungol
Piperazine, (+)-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-
Piperazine, (+/-)-1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel-
Piperazine, 1-acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-, cis-
Prestwick0_000389
Prestwick1_000389
Prestwick2_000389
Prestwick3_000389
Prestwick_744
R 41,400
R 41400
R-41400
R41,400
R41400
SAM001246983
SMR000058460
SPBio_002498
Tocris-1103
UC280_SIGMA
UPCMLD-DP138
UPCMLD-DP138:001
Xolegel
ATC-Codes:
Side-Effects:
Side-EffectFrequency
abdominal pain0
nausea0
pain0
papilledema0
paresthesia0
pruritus0
swelling0
thrombocytopenia0
erythema0
urticaria0
vomiting0
chills0
photophobia0
pyogenic granuloma0
dry skin0
scalp seborrhea0
eye swelling0
acne0
leukopenia0
keratoconjunctivitis sicca0
alopecia0
anaphylaxis0
hemolytic anemia0
arrhythmia0
dermatitis0
contact dermatitis0
diarrhea0
dizziness0
somnolence0
rash0
fever0
gynecomastia0
headache0
hypersensitivity0
hypertriglyceridemia0
impetigo0
impotence0
allergic reaction0

Target

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Uniprot ID:CP3A4_HUMAN
Synonyms:
Albendazole monooxygenase
Albendazole sulfoxidase
CYPIIIA3
CYPIIIA4
Cytochrome P450 3A3
Cytochrome P450 3A4
HLp
NF-25
Nifedipine oxidase
P450-PCN1
Quinine 3-monooxygenase
Taurochenodeoxycholate 6-alpha-hydroxylase
EC-Numbers:1.14.13.32
1.14.13.67
1.14.13.97
Organism:Homo sapiens
Human
PDB IDs:1TQN 1W0E 1W0F 1W0G 2J0D 2V0M
Structure:
2V0M

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----
----
----
----
----
----
----
--4-
--11-
--13-
--16-
--17-
--20-
--22-
--40-
--50-
--57-
--72-
--72-
24---
30---
--2E2-
--210-
--245-
--720-
--786.0-
--57000-

References:

10048600
12072427
12624000
12817528
1371482
14712470
15821046
8690825
Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo.. L L von Moltke; D J Greenblatt; S X Duan; J S Harmatz; C E Wright; R I Shader (1996) Journal of clinical psychopharmacology display abstract
Biotransformation of the H-1 antagonist terfenadine to its desalkyl and hydroxy metabolites was studied in vitro using microsomal preparations of human liver. These metabolic reactions are presumed to be mediated by Cytochrome P450-3A isoforms. The azole antifungal agent ketoconazole was a highly potent inhibitor of both reactions, having mean inhibition constants (Ki) of 0.037 and 0.34 microM for desalkyl- and hydroxy-terfenadine formation, respectively. Itraconazole also was a potent inhibitor, with Ki values of 0.28 and 2.05 microM, respectively. Fluconazole, on the other hand, was a weak inhibitor. Six selective serotonin reuptake inhibitor antidepressants tested in this system were at least 20 times less potent inhibitors of terfenadine metabolism than was ketoconazole. An in vitro-in vivo scaling model used in vitro Ki values, typical clinically relevant plasma concentrations of inhibitors, and presumed liver:plasma partition ratios to predict the degree of terfenadine clearance impairment during coadministration of terfenadine with these inhibitors in humans. The model predicted a large and potentially hazardous impairment of terfenadine clearance by ketoconazole and, to a slightly lesser extent, by itraconazole. However, fluconazole and the six selective serotonin reuptake inhibitors (SSRIs) at usual clinical doses were not predicted to impair terfenadine clearance to a degree that would be of clinical importance. Caution is nonetheless warranted with the coadministration of SSRIs and terfenadine when high doses of SSRIs (particularly fluoxetine) are administered. Also, some individuals may be unusually susceptible to metabolic inhibition for a variety of reasons.
9616194
Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources.. S Rotzinger; J Fang; G B Baker (1998) Drug metabolism and disposition: the biological fate of chemicals display abstract
The metabolism of the antidepressant drug trazodone to its active metabolite, m-chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomal preparations and cDNA-expressed human cytochrome P450 (P450) enzymes. The kinetics of mCPP formation from trazodone were determined, and three in vitro experiments were performed to identify the major P450 enzyme involved. Trazodone (100 microM) was incubated with 16 different human liver microsomal preparations characterized for activities of 7 different P450 isoforms. The production of mCPP correlated significantly with activity of cytochrome P4503A4 (CYP3A4) only. Trazodone (100 microM) was then incubated with microsomes from cells expressing human CYP1A1, CYP1A2, CYP2C8, CYP2C9arg, CYP2C9cys, CYP2C19, CYP2D6, or CYP3A4. Only incubations with CYP3A4 resulted in mCPP formation. In the third experiment, the CYP3A4 inhibitor ketoconazole was found to inhibit mCPP formation concentration dependently in both human liver microsomes and in microsomes from cells expressing human CYP3A4. The present results indicate that trazodone is a substrate for CYP3A4, that CYP3A4 is a major isoform involved in the production of mCPP from trazodone, and that there is the possibility of drug-drug interactions with trazodone and other substrates, inducers and/or inhibitors of CYP3A4.
SuperCyp