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Drug-Target Interaction

Drug

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PubChem ID:65906
Structure:
Synonyms:
108612-45-9
2-((1-(1-(p-Fluorobenzyl)-2-benzimidazolyl)-4-piperidyl)methylamino)-4(3H)
2-((1-(1-(p-Fluorobenzyl)-2-benzimidazolyl)-4-piperidyl)methylamino)-4(3H)-pyrimidinone
4(1H)-Pyrimidinone, 2-((1-(1-((4-fluorophenyl)methyl)-1H-benzimidazol-2-yl)-4-piperidinyl)methylamino)-
C24H25FN6O
D01117
KS-1139
LS-135935
Mizolastina [INN-Spanish]
Mizolastine
Mizolastine (JAN/INN)
Mizolastine [INN]
Mizolastinum [INN-Latin]
Mizolen
Mizollen
Mizollen (TN)
MKC-431
NCGC00181013-01
SL 85.0324
SL-85.0324
ZINC13831810
Zolim
Zolistam
Zolistan
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:

10597902
In vitro inhibition of human liver drug metabolizing enzymes by second generation antihistamines.. J M Nicolas; R Whomsley; P Collart; J Roba (1999) Chemico-biological interactions display abstract
Cetirizine, terfenadine, loratadine, astemizole and mizolastine were compared for their ability to inhibit marker activities for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and for some glucuronidation isoenzymes in human liver microsomes. The most pronounced effects were observed with terfenadine, astemizole and loratadine which inhibited CYP3A4-mediated testosterone 6beta-hydroxylation (IC50 of 23, 21 and 32 microM, respectively) and CYP2D6-mediated dextromethorphan O-demethylation (IC50 of 18, 36 and 15 microM, respectively). In addition, loratadine markedly inhibited the CYP2C19 marker activity, (S)-mephenytoin 4-hydroxylation (Ki of 0.17 microM). Furthermore, loratadine activated the CYP2C9-catalyzed tolbutamide hydroxylation (ca. 3-fold increase at 30 microM) and inhibited some glucuronidation enzymes. Mizolastine appeared to be a relatively weak and unspecific inhibitor of CYP2E1, CYP2C9, CYP2D6 and CYP3A4 (IC50Ss in the 100 micromolar range). Cetirizine demonstrated no effect on the investigated activities. A comparison of the inhibitory potencies of cetirizine, terfenadine, loratidine, astemizole and mizolastine with their corresponding plasma concentrations in humans suggests that these antihistamines are not likely to interfere with the metabolic clearance of coadministered drugs, with the exception of loratidine, which appears to inhibit CYP2C19 with sufficient potency to warrant additional investigation.
11510627