Smallest Maximum Intramolecular Distance: A Novel Method to Mitigate Pregnane Xenobiotic Receptor Activation.
Michael J BowerAlex M AronovThomas ClevelandNiresh HariparsadGeorgia B McGaugheyDaniel R McMastersXiaodan ZhangBrian GoldmanPublished 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.