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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:CP2B6_HUMAN
Synonyms:
CYPIIB6
Cytochrome P450 2B6
P450 IIB1
EC-Numbers:1.14.14.1
Organism:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

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

References:

17164692
Mechanisms of venoocclusive disease resulting from the combination of cyclophosphamide and roxithromycin.. Priska Kaufmann; Manuel Haschke; Michael Török; Johannes Beltinger; Katrijn Bogman; Markus Wenk; Luigi Terracciano; Stephan Krähenbühl (2006) Therapeutic drug monitoring display abstract
BACKGROUND: High doses (>or=500 mg/m) of cyclophosphamide are known to cause venoocclusive disease (VOD). The authors recently observed a patient treated with immunosuppressive cyclophosphamide doses (100 mg/day) and roxithromycin who developed VOD. Because roxithromycin inhibits cytochrome P450 (CYP) 3A4 and P-glycoprotein, the patient may have been exposed to higher cyclophosphamide and/or cyclophosphamide metabolite concentrations. METHODS: The effect of roxithromycin on the metabolism and toxicity of cyclophosphamide was studied using human hepatic microsomes and a human endothelial cell line. RESULTS: Cyclophosphamide or roxithromycin at concentrations from 0.05 to 500 micromol/L were not toxic to endothelial cells as assessed by lactate dehydrogenase (LDH) leakage assay. However, the combination of roxithromycin (500 micromol/L) and cyclophosphamide was toxic for all the tested cyclophosphamide concentrations (0.05 to 500 micromol/L) without clear concentration dependence (LDH ratio 38.3 +/- 11.0 [mean +/- SEM] for the combination with cyclophosphamide 0.05 micromol/L and 50.2 +/- 10.2 for the combination with cyclophosphamide 500 micromol/L; P
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.