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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:CP3A5_HUMAN
Synonyms:
CYPIIIA5
Cytochrome P450 3A5
HLp2
P450-PCN3
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

12814972
In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5.. Kiran C Patki; Lisa L Von Moltke; David J Greenblatt (2003) Drug metabolism and disposition: the biological fate of chemicals display abstract
Midazolam, triazolam (TRZ), testosterone, and nifedipine have all been widely used as probes for in vitro metabolism of CYP3A. We used these four substrates to assess the contributions of CYP3A4 and CYP3A5 to in vitro biotransformation in human liver microsomes (HLMs) and in recombinant enzymes. Recombinant CYP3A4 and CYP3A5 (rCYP3A4 and rCYP3A5) both produced 1-OH and 4-OH metabolites from midazolam and triazolam, 6 beta-hydroxytestosterone from testosterone, and oxidized nifedipine from nifedipine. Overall, the metabolic activity of CYP3A5 was less than that of CYP3A4. Ketoconazole potently inhibited midazolam, triazolam, testosterone, and nifedipine metabolite formation in HLMs and in rCYP3A4. The inhibitory potency of ketoconazole in rCYP3A5 was about 5- to 19-fold less than rCYP3A4 for all four substrates. In testosterone interaction studies, testosterone inhibited 1-OH-TRZ formation, but significantly activated 4-OH-TRZ formation in HLMs and rCYP3A4 but not in rCYP3A5. Oxidized nifedipine formation was inhibited by testosterone in rCYP3A4. However, in rCYP3A5, testosterone slightly activated oxidized nifedipine formation at lower concentrations, followed by inhibition. Thus, CYP3A4 and CYP3A5 both contribute to midazolam, triazolam, testosterone, and nifedipine biotransformation in HLMs, with CYP3A5 being metabolically less active than CYP3A4 in general. Because the inhibitory potency of ketoconazole in rCYP3A5 is substantially less than in rCYP3A4 and HLMs, CYP3A5 is probably less important than CYP3A4 in drug-drug interactions involving ketoconazole and CYP3A substrates.
1371482
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.