Pub. Date : 2020 Mar 15
PMID : 32044230
3 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4. | Ritonavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 2 | We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent CYP3A4 inhibitor marketed as pharmacoenhancer. | Ritonavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 3 | Analysis of compounds with the R1 side-group as phenyl or naphthalene and R2 as indole or naphthalene in different stereo configuration showed that (i) analogues with the R2-naphthalene tend to bind tighter and inhibit CYP3A4 more potently than the R2-phenyl/indole containing counterparts; (ii) stereochemistry becomes a more important contributing factor, as the bulky side-groups limit the ability to optimize protein-ligand interactions; (iii) the relationship between the R1/R2 configuration and preferential binding to CYP3A4 is complex and depends on the side-group functionality/interplay and backbone spacing; and (iv) three inhibitors, 5a-b and 7d, were superior to ritonavir (IC50 of 0.055-0.085 muM vs. 0.130 muM, respectively). | Ritonavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |