A combinatorial approach for the discovery of cytochrome P450 2D6 inhibitors from nature.

摘要: The human cytochrome P450 2D6 (CYP2D6) enzyme is part of phase-I metabolism and metabolizes at least 20% all clinically relevant drugs. Therefore, it an important target for drug-drug interaction (DDI) studies. High-throughput screening (HTS) assays are commonly used tools to examine DDI, but show certain drawbacks with regard their applicability natural products. We propose in silico – vitro workflow the reliable identification products CYP2D6 inhibitory potential. In order identify candidates from product-based databases that share similar structural features established inhibitors, a pharmacophore model was applied. virtual hits were tested inhibition recombinant bioluminescence-based assay. By controlling unspecific interferences test compounds detection reaction, number false positives reduced. success rate reported 76%, as most identified approach able inhibit activity. summary, presented here suitable cost-efficient strategy discovery new inhibitors product libraries.