Smallest Maximum Intramolecular Distance: A Novel Method to Mitigate Pregnane Xenobiotic Receptor Activation.

Michael J BowerAlex M AronovThomas ClevelandNiresh HariparsadGeorgia B McGaughey Daniel R McMastersXiaodan ZhangBrian Goldman

Published in: Journal of chemical information and modeling (2020)

Induction of cytochrome P450 isoform 3A4 via activation of the pregnane xenobiotic receptor (PXR) is a concern for pharmaceutical discovery and development, as it can lead to drug-drug interactions. We present a novel molecular descriptor, the smallest maximum intramolecular distance (SMID), which is correlated with PXR activation, and a method for using the SMID descriptor to guide discovery chemists in modifying lead compounds to decrease PXR activation.

Keyphrases

small molecule
high throughput
emergency department
energy transfer
single cell
quantum dots