Bagdanoff, Jeffrey, Xu, Yongjin, Dollinger, Gavin and Martin, Eric (2015) Effect of Chirality on Common in Vitro Experiments: An Enantiomeric Pair Analysis. Journal of Medicinal Chemistry, 58 (15). pp. 5781-5788. ISSN 1520-4804

Abstract

This analysis elucidates the impact of small molecule architecture on common in vitro ADME assays. In vitro parameters considered in this analysis included Caco-2 permeability/efflux, CYP3A4 inhibition, hERG inhibition, and rat microsomal extraction ratio (ER). The statistical significance and practical meaningfulness of chirality were determined by comparison of the distribution of enantiomers with the experimental variation distribution observed from duplicate measurements. Statistical tools were applied to characterize the role of molecular architecture on the outcome of a given in vitro assay. We found that CYP3A4 inhibition, hERG inhibition, Caco-2 permeability, and efflux are unlikely to be modulated by chirality. However, rat microsomal ER provides a statistically significant, and quantitatively meaningful, chance of being influenced by chirality.

Item Type:	Article
Date Deposited:	28 Nov 2017 00:45
Last Modified:	25 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/24698