Current status and future directions of high-throughput ADME screening in drug discovery

Abstract

During the last decade high-throughput in vitro absorption, distribution, metabolism and excretion (HT-ADME) screening has become an essential part of any drug discovery effort of synthetic molecules. The conduct of HT-ADME screening has been "industrialized" due to the extensive development of software and automation tools in cell culture, assay incubation, sample analysis and data analysis. The HT-ADME assay portfolio continues to expand in emerging areas such as drug-transporter interactions, early soft spot identification, and ADME screening of peptide drug candidates. Additionally, thanks to the very large and high-quality HT-ADME data sets available in many biopharma companies, in silico prediction of ADME properties using machine learning has also gained much momentum in recent years. In this review, we discuss the current state-of-the-art practices in HT-ADME screening including assay portfolio, assay automation, sample analysis, data processing, and prediction model building. In addition, we also offer perspectives in future development of this exciting field.

Keywords: Acoustic ejection mass spectrometry; Automation; Bioanalysis; HT-ADME; In vitro; Mass spectrometry.

Graphical abstract

Fig. 1

Centralized SRM database allows sharing of MS/MS conditions across multiple sites and instrument platforms using DiscoveryQuant™. SRM: selected reaction monitoring. Instrument pictures are used with permission from Sciex.

Fig. 2

Schematic of the acoustic ejection mass spectrometer (AEMS) system. Reprinted with permission from Refs. [76], Copyright (2020) American Chemical Society.