In silico approaches to predict drug-transporter interaction profiles

Author(s)
Sankalp Jain, Gerhard F. Ecker
Abstract

Transport proteins play a crucial role in drug distribution, disposition, and clearance by mediating cellular drug influx and efflux. Inhibition of these transporters may lead to drug-drug interactions or even drug-induced liver injury, such as cholestasis, which comprises a major challenge in drug development process. Thus, computer-based (in silico) models that can predict the pharmacological and toxicological profiles of these small molecules with respect to liver transporters may help in the early prioritization of compounds and hence may lower the high attrition rates. In this chapter, we provide a protocol for in silico prediction of cholestasis by generating validated predictive models. In addition to the two-dimensional molecular descriptors, we include transporter inhibition predictions as descriptors and evaluate the influence of the same on the performance of the cholestasis models.

Organisation(s)
Pages
383-396
No. of pages
14
DOI
https://doi.org/10.1007/978-1-4939-9420-5_26
Publication date
01-2019
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry
Keywords
ASJC Scopus subject areas
Molecular Biology, Genetics
Portal url
https://ucrisportal.univie.ac.at/en/publications/in-silico-approaches-to-predict-drugtransporter-interaction-profiles(3f3feed4-5928-48bb-a731-07977476c41c).html