English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The cytochrome P450s (CYPs) play a central role in the metabolism of various endogenous and exogenous compounds including drugs. CYPs are vulnerable to inhibition and induction which can lead to adverse drug reactions. Therefore, insights into the underlying mechanism of CYP450 inhibition and the estimation of overall CYP inhibitor properties might serve as valuable tools during the early phases of drug discovery. Herein, we present a large data set of inhibitors against five major metabolic CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) for the evaluation of important physicochemical properties and ligand efficiency metrics to define property trends across various activity levels (active, efficient and inactive). Decision tree models for CYP inhibition were developed with an accuracy >90% for both the training set and 10-folds cross validation. Overall, molecular weight (MW), hydrogen bond acceptors/donors (HBA/HBD) and lipophilicity (clogP/logPo/w) represent important physicochemical descriptors for CYP450 inhibitors. However, highly efficient CYP inhibitors show mean MW, HBA, HBD and logP values between 294.18–482.40,5.0–8.2,1–7.29 and 1.68–2.57, respectively. Our results might help in optimization of toxicological profiles associated with new chemical entities (NCEs), through a better understanding of inhibitor properties leading to CYP-mediated interactions.

computation

Exploring the Chemical Space of Cytochrome P450 Inhibitors Using Integrated Physicochemical Parameters, Drug Efficiency Metrics and Decision Tree Models