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Drug-Target Interaction

Drug

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PubChem ID:63009
Structure:
Synonyms:
(1S,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride
(1S,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride
(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-ami
(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride
(1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride
1-Naphthalenamine, 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-, hydrochloride, (1S-cis)-
1-Naphthalenamine, 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-, hydrochloride,(1S-cis)-
1-naphthalenamine,1,2,3,4-tetrahydro-4-(3,4-dichlorophenyl)-N-methyl-,(1S-cis)-
79559-97-0
79617-96-2
Ambap2474
Aremis
Atruline
C17H17Cl2N.HCl
Cp 51,974-1
CP-51974-1
CP-5197401
CPD000466298
D00825
EU-0100870
Gladem
LS-94166
Lustral
MLS000758929
MLS001401398
NCGC00092386-01
S6319_SIGMA
SAM001246666
SAM001247100
Serad
Serlift
Sertraline
Sertraline hydrochloride
Sertraline Hydrochloride (1S-cis)-Isomer
Sertraline hydrochloride (JAN/USAN)
Sertraline hydrochloride [USAN]
Sertraline.HCl
SMR000466298
SPECTRUM1505262
Tatig
TL8005382
Tresleen
Zoloft
Zoloft (TN)
ATC-Codes:

Target

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Uniprot ID:CP2C9_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC9
Cytochrome P450 2C9
P-450MP
P450 MP-4/MP-8
P450 PB-1
S-mephenytoin 4-hydroxylase
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:1OG2 1OG5 1R9O
Structure:
1R9O

Binding Affinities:

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

References:

10510155
11420570
15547048
Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study.. R Scott Obach; Loretta M Cox; Larry M Tremaine (2005) Drug metabolism and disposition: the biological fate of chemicals display abstract
The oxidative and conjugative metabolism of sertraline was examined in vitro to identify the enzymes involved in the generation of N-desmethyl, deaminated, and N-carbamoyl-glucuronidated metabolites in humans. In human liver microsomes, sertraline was N-demethylated and deaminated by cytochrome P450 (P450) enzymes with overall K(m) values of 98 and 114 microM, respectively, but the intrinsic clearance for N-demethylation was approximately 20-fold greater than for deamination. Using P450 isoform-selective inhibitors and recombinant heterologously expressed enzymes, it was demonstrated that several P450 enzymes catalyzed sertraline N-demethylation, with CYP2B6 contributing the greatest extent, and lesser contributions from CYP2C19, CYP2C9, CYP3A4, and CYP2D6. For deamination, data supported a role for CYP3A4 and CYP2C19. Purified human monoamine oxidases A and B also catalyzed sertraline deamination with comparable K(m) values (230-270 microM). Monoamine oxidase B catalyzed the reaction approximately 3-fold faster than did monoamine oxidase A. Sertraline N-carbamoyl glucuronidation was measured in human liver microsomes in bicarbonate buffer and under a CO2 atmosphere (K(m) = 50 microM) and was catalyzed at the fastest rate by recombinant human UGT2B7. The observation that multiple enzymes appear to be involved in sertraline metabolism suggests that there should be no single agent that could substantially alter the pharmacokinetics of sertraline, nor should there be any single drug-metabolizing enzyme genetic polymorphism (e.g., CYP2D6, CYP2C19, CYP2C9, UGT1A1) that could profoundly impact the pharmacokinetics of sertraline.
8861776
9384467
Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation.. J Schmider; D J Greenblatt; L L von Moltke; D Karsov; R I Shader (1997) British journal of clinical pharmacology display abstract
AIMS: Inhibition of cytochrome P450 (CYP) activity by selective serotonin reuptake inhibitors (SSRIs) has frequently been reported with regard to pathways mediated by CYP2D6, CYP3A4/5, and CYP1A2. Little data exist on the capability of SSRIs to inhibit CYP2C9. METHODS: We investigated the effect of SSRIs on p-hydroxylation of phenytoin (PPH), an established index reaction reflecting CYP2C9 activity, in an in vitro assay using liver tissue from six different human donors. RESULTS: In control incubations (without inhibitor), 5-(p-hydroxy-phenyl)-5-phenylhydantoin (HPPH) formation rates were: Vmax 0.023 nmol min(-1) mg(-1); Km 14.3 microM. Average inhibition constants (Ki) differed significantly among the SSRIs, with fluvoxamine having the lowest Ki (6 microM) followed by R-fluoxetine (13 microM), norfluoxetine (17 microM), RS-fluoxetine (19 microM), sertraline (33 microM), paroxetine (35 microM), S-fluoxetine (62 microM), and desmethylsertraline (66 microM). Thus, assuming comparable molar concentrations at the site of inhibition, fluvoxamine can be expected to have the highest probability of interfering with the metabolism of CYP2C9 substrates. S-fluoxetine is on average a 5 fold weaker CYP2C9 inhibitor than either R-fluoxetine or the racemic mixture. CONCLUSIONS: These findings are consistent with published case reports describing SSRI-related increments in plasma phenytoin levels. Because phenytoin has a narrow therapeutic index, plasma levels should be closely monitored when SSRIs are coadministered.
9808080