The development of novel cytochrome P450 2J2 (CYP2J2) inhibitor and the underlying interaction between inhibitor and CYP2J2

Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels CYP2J2 have been associated with various types cancer, and therefore it serves potential drug target. Herein, using high-throughput screening approach based on enzymic activity CYP2J2, we rapidly effectively identified novel natural inhibitor (Piperine, 9a) IC50 value 0.44 μM from 108 common herbal medicines. Next, series its derivatives were designed synthesised the underlying interactions Piperine CYP2J2. As expected, much stronger inhibitors 9k 9l developed their inhibition activities increased about 10 folds than values 40 50 nM, respectively. Additionally, kinetics illustrated competitive towards Ki calculated to be 0.11 0.074 μM, Furthermore, detailed interaction mechanism was explicated by docking molecular dynamics, our results revealed residue Thr114 Thr 315 critical sites action, moreover spatial distance between carbon atom ligand methylene Fe iron porphyrin coenzyme vital factor human