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Drug-Target Interaction

Drug

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PubChem ID:444037
Structure:
Synonyms:
(3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-(dimethylamino)-3-h
(3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)-6-[(2S,3R,4S,6R)-4-dimethylamino-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-10-(2-methoxyethoxymethoxyimino)-3,5,7,9,11,13-hexamethyl-1-oxacyclotetradecan-2-one
AC1L9FLG
BCBcMAP01_000131
DB00778
DivK1c_000382
HMS2236F08
KBio1_000382
KBio2_002133
KBio2_004701
KBio2_007269
KBio3_002217
KBioGR_000779
KBioSS_002133
MLS001304008
NINDS_000382
Roxithromycin
SMP1_000054
SMR000718779
SPBio_001422
Spectrum2_001551
Spectrum3_001159
Spectrum4_000200
Spectrum_001653
ATC-Codes:

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:
----
----
----
----

References:

16595573
8948090
9806945
Comparative studies of in vitro inhibition of cytochrome P450 3A4-dependent testosterone 6beta-hydroxylation by roxithromycin and its metabolites, troleandomycin, and erythromycin.. H Yamazaki; T Shimada (1998) Drug metabolism and disposition: the biological fate of chemicals display abstract
Roxithromycin has been shown to be a relatively weak inhibitor of cytochrome P450 (P450 or CYP)-dependent drug oxidations, compared with troleandomycin. The potential for roxithromycin and its major metabolites found in human urine [namely the decladinosyl derivative (M1), O-dealkyl derivative (M2), and N-demethyl derivative (M3)] to inhibit testosterone 6beta-hydroxylation after metabolic activation by CYP3A4 was examined and compared with inhibition by troleandomycin and erythromycin in vitro. Of roxithromycin and its studied metabolites, M3 was the most potent in inhibiting CYP3A4-dependent testosterone 6beta-hydroxylation by human liver microsomes and was activated to the inhibitory P450.Fe2+-metabolite complex to the greatest extent. Roxithromycin and its metabolites were N-demethylated by human liver microsomes, although the rates were slower than those measured with troleandomycin and erythromycin as substrates. Recombinant human CYP3A4 in a baculovirus system coexpressing NADPH-P450 reductase was very active in catalyzing the N-demethylation of roxithromycin, M1, and M2, as well as troleandomycin, erythromycin, and M3. The order for inhibition of CYP3A4-dependent testosterone 6beta-hydroxylation activities by these macrolide antibiotics in the recombinant CYP3A4 system was estimated to be troleandomycin > erythromycin >/= M3 >/= M2 > M1 >/= roxithromycin. Erythromycin, roxithromycin, and its metabolites all failed to inhibit CYP1A2-dependent (R)-warfarin 7-hydroxylation and CYP2C9-dependent (S)-warfarin 7-hydroxylation but did inhibit CYP3A4-dependent (R)-warfarin 7-hydroxylation. These results suggest that roxithromycin itself is not as potent an inhibitor of CYP3A4 activities as are troleandomycin and erythromycin, probably because of the slower metabolism of this compound to metabolites M1, M2, and M3 in humans.
9806945
Comparative studies of in vitro inhibition of cytochrome P450 3A4-dependent testosterone 6beta-hydroxylation by roxithromycin and its metabolites, troleandomycin, and erythromycin.. H Yamazaki; T Shimada (1998) Drug metabolism and disposition: the biological fate of chemicals display abstract
Roxithromycin has been shown to be a relatively weak inhibitor of cytochrome P450 (P450 or CYP)-dependent drug oxidations, compared with troleandomycin. The potential for roxithromycin and its major metabolites found in human urine [namely the decladinosyl derivative (M1), O-dealkyl derivative (M2), and N-demethyl derivative (M3)] to inhibit testosterone 6beta-hydroxylation after metabolic activation by CYP3A4 was examined and compared with inhibition by troleandomycin and erythromycin in vitro. Of roxithromycin and its studied metabolites, M3 was the most potent in inhibiting CYP3A4-dependent testosterone 6beta-hydroxylation by human liver microsomes and was activated to the inhibitory P450.Fe2+-metabolite complex to the greatest extent. Roxithromycin and its metabolites were N-demethylated by human liver microsomes, although the rates were slower than those measured with troleandomycin and erythromycin as substrates. Recombinant human CYP3A4 in a baculovirus system coexpressing NADPH-P450 reductase was very active in catalyzing the N-demethylation of roxithromycin, M1, and M2, as well as troleandomycin, erythromycin, and M3. The order for inhibition of CYP3A4-dependent testosterone 6beta-hydroxylation activities by these macrolide antibiotics in the recombinant CYP3A4 system was estimated to be troleandomycin > erythromycin >/= M3 >/= M2 > M1 >/= roxithromycin. Erythromycin, roxithromycin, and its metabolites all failed to inhibit CYP1A2-dependent (R)-warfarin 7-hydroxylation and CYP2C9-dependent (S)-warfarin 7-hydroxylation but did inhibit CYP3A4-dependent (R)-warfarin 7-hydroxylation. These results suggest that roxithromycin itself is not as potent an inhibitor of CYP3A4 activities as are troleandomycin and erythromycin, probably because of the slower metabolism of this compound to metabolites M1, M2, and M3 in humans.