TICBase: Integrated Resource for Data on Drug and Environmental Chemical Interactions with Mammalian Drug Transporters

Abstract

Environmental health science seeks to predict how environmental toxins, chemical toxicants, and prescription drugs accumulate and interact within the body. Xenobiotic transporters of the ATP‐binding Cassette (ABC) and solute carrier (SLC) superfamilies are major determinants of the uptake and disposition of xenobiotics across the kingdoms of life. The goal of this study was to integrate drug and environmental chemical interactions (DECIs) of mammalian ABC and SLC proteins in a centralized, integrative database. We built upon an existing publicly accessible platform – the “TransPortal” – which was updated with novel data and searchable features on transporter‐interfering chemicals (TICs) from manually curated literature data. The integrated resource TransPortal‐TICBase (https://transportal.compbio.ucsf.edu) now contains information on 46 different mammalian xenobiotic transporters of the ABC‐ and SLC‐type superfamilies, including 13 newly added rodent and two additional human drug transporters, 126 clinical drug‐drug interactions (DDIs), and a more than quadrupled expansion of the initial in vitro chemical interaction data from 1402 to 6296 total interactions. Based on our updated database, environmental interference with major human and rodent drug transporters occurs across the ABC‐ and SLC‐type superfamilies, with kinetics indicating that some chemicals, such as the ionic liquid 1‐hexylpyridinium chloride and the antiseptic chlorhexidine, can act as strong inhibitors with potencies similar or even higher than pharmacological model inhibitors. The new integrated web portal serves as a central repository of current and emerging data for interactions of prescription drugs and environmental chemicals with human drug transporters. This archive has important implications for predicting adverse drug‐drug and drug‐environmental chemical interactions and can serve as a reference website for the broader scientific community of clinicians and researchers.