Pub. Date : 2021
PMID : 34272716
9 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | In evaluating a time-saving assay using diclofenac as the CYP2C9 probe substrate, a discrepancy was observed in which minimal inhibition was detected using diclofenac whereas using (S)-warfarin resulted in potent inhibition, supporting the presence of dual-binding sites in the relatively large CYP2C9 active site cavity.These observations provided further insights into explaining the reported ineffective inactivation of CYP2C9 for the pan-CYP inactivator 1-aminobenzotriazole (ABT). | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 2 | In evaluating a time-saving assay using diclofenac as the CYP2C9 probe substrate, a discrepancy was observed in which minimal inhibition was detected using diclofenac whereas using (S)-warfarin resulted in potent inhibition, supporting the presence of dual-binding sites in the relatively large CYP2C9 active site cavity.These observations provided further insights into explaining the reported ineffective inactivation of CYP2C9 for the pan-CYP inactivator 1-aminobenzotriazole (ABT). | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 3 | In evaluating a time-saving assay using diclofenac as the CYP2C9 probe substrate, a discrepancy was observed in which minimal inhibition was detected using diclofenac whereas using (S)-warfarin resulted in potent inhibition, supporting the presence of dual-binding sites in the relatively large CYP2C9 active site cavity.These observations provided further insights into explaining the reported ineffective inactivation of CYP2C9 for the pan-CYP inactivator 1-aminobenzotriazole (ABT). | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 4 | Mechanistic reversible and time-dependent inhibition experiments revealed that the ineffective CYP2C9 inactivation by ABT was also probe-dependent, with utilization of (S)-warfarin as the probe substrate resulting in more potent CYP2C9 inhibition by ABT compared to diclofenac. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 5 | Addition of (S)-warfarin to the reversible and time-dependent inhibition experiments between ABT and diclofenac resulted in an attenuation of the inhibitory effects of ABT on CYP2C9-mediated diclofenac metabolism. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 6 | Addition of (S)-warfarin to the reversible and time-dependent inhibition experiments between ABT and diclofenac resulted in an attenuation of the inhibitory effects of ABT on CYP2C9-mediated diclofenac metabolism. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 7 | Molecular docking studies further confirmed that (S)-warfarin and diclofenac preferentially bind in different regions of the CYP2C9 active site, with (S)-warfarin occupying a distal "warfarin-binding pocket" and diclofenac occupying a binding site close to the active heme moiety. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 8 | Molecular docking studies further confirmed that (S)-warfarin and diclofenac preferentially bind in different regions of the CYP2C9 active site, with (S)-warfarin occupying a distal "warfarin-binding pocket" and diclofenac occupying a binding site close to the active heme moiety. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 9 | ABT preferentially binds in the distal warfarin-binding pocket, supporting that diclofenac is minimally deterred from access to the CYP2C9 active site in the presence of ABT, thus resulting in minimal inactivation. | Diclofenac | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |