Pub. Date : 1998 Sep
PMID : 9733666
10 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Interaction of terfenadine and its primary metabolites with cytochrome P450 2D6. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 2 | The substrate structure-activity relationships described for the major human drug-metabolizing cytochrome P450 (P450 or CYP) enzymes suggest that the H1 receptor antagonist terfenadine could interact with CYP2D6 either as a substrate or as an inhibitor, in addition to its known ability to act as a substrate for CYP3A4. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 3 | Based on this substrate structure-activity relationship, computer modeling studies were undertaken to explore the likely interactions of terfenadine with CYP2D6. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 4 | An overlay of terfenadine and dextromethorphan, a known substrate of CYP2D6, showed that it was possible to superimpose the site of hydroxylation (t-butyl group) and the nitrogen atom of terfenadine with similar regions in dextromethorphan. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 5 | An overlay of terfenadine and dextromethorphan, a known substrate of CYP2D6, showed that it was possible to superimpose the site of hydroxylation (t-butyl group) and the nitrogen atom of terfenadine with similar regions in dextromethorphan. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 6 | These observations were substantiated by the ease of docking of terfenadine into a protein model of CYP2D6. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 7 | Experimentally, terfenadine inhibited CYP2D6 activity in human liver microsomes with an IC50 of 14-27 microM, depending on the CYP2D6 substrate used. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 8 | Experimentally, terfenadine inhibited CYP2D6 activity in human liver microsomes with an IC50 of 14-27 microM, depending on the CYP2D6 substrate used. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 9 | The inhibition of CYP2D6 was further defined by determining the Ki for terfenadine against bufuralol 1"-hydroxylase activity in four human livers. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 10 | These data indicate that, as predicted from modeling studies, terfenadine has the structural features necessary for interaction with CYP2D6. | Terfenadine | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |