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

ABSTRACT: Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels of CYP2J2 have been associated with various types of cancer, and therefore it serves as a potential drug target. Herein, using a high-throughput screening approach based on enzymic activity of CYP2J2, we rapidly and effectively identified a novel natural inhibitor (Piperine, 9a) with IC₅₀ value of 0.44 μM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine wit

SUBMITTER: Tian X 

PROVIDER: S-EPMC7946002 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature