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Smallest Maximum Intramolecular Distance: A Novel Method to Mitigate Pregnane Xenobiotic Receptor Activation
journal contribution
posted on 2020-03-16, 18:09 authored by Michael
J. Bower, Alex M. Aronov, Thomas Cleveland, Niresh Hariparsad, Georgia B. McGaughey, Daniel R. McMasters, Xiaodan Zhang, Brian GoldmanInduction 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.