High-Throughput ADME Screening Services for Stroke Drug Discovery and Development

A large number of hits are now routinely identified by screening compound collections and gene family libraries, increasing the need for high-throughput absorption, distribution, metabolism, and elimination (ADME) assays. In order to identify chemotypes and lead compounds with favorable pharmacokinetic and toxicological profiles, studies to evaluate ADME are initiated early in the stroke drug discovery process. Based on the widespread use of liquid chromatography/mass spectrometry (LC-MS) and liquid chromatography/tandem mass spectrometry (LC-MS/MS), many ADME assays can be run in a high-throughput manner. High-throughput in vitro ADME screening is an important part of stroke lead compound optimization.

Fig. 1. Bioanalytical approaches for high-throughput ADME screening in drug discovery. (Shou et al., 2020)

Custom High-Throughput ADME Screening Services

Ace Therapeutics's high-throughput ADME (HT-ADME) screening platform is staffed by a team of experienced experts in stroke research and drug development. We offer HT-ADME packages using state-of-the-art instrumentation and methodologies such as automated liquid handling, high-speed liquid chromatography-tandem mass spectrometry (LC-MS/MS) for sample analysis, as well as software and automation tools to accelerate the stroke lead compound optimization and drug discovery process.

Our HT-ADME laboratory works with pharmaceutical clients around the world to perform large-scale ADME screening assays using in-house or customized protocols.

HT-ADME screening assay portfolio:

• Thermodynamic and kinetic assays
• Metabolic stability assays
• Caco-2 permeability assays
• Protein binding assays (plasma, tissue, microsomal)
• Erythrocyte partitioning assays
• Stroke drug transporter protein interaction analysis
• Early soft spot identification
• CYP inhibition
• ADME screening of peptide drug candidates for stroke

Workflow of HT-ADME Screening

Step Ⅰ

Plate administration of test compounds: We test compounds onto a high-density plate format (96, 384, or even 1536-well plates) or others suitable format. Plate management ensures that test compounds are properly labeled and tracked throughout the screening process.

Step Ⅱ

Optimization of MS/MS methods: We optimize MS/MS methods, including parameters such as ionization mode, collision energy, and chromatographic conditions, to achieve optimal sensitivity, selectivity, and accuracy for the detection and quantification of test compounds.

Step Ⅲ

In vitro ADME experiments and sample clean-up: We perform various in vitro experiments on test compounds to evaluate their absorption, distribution, metabolism, and excretion properties. At the end of the experiments, samples are typically subjected to sample clean-up procedures to remove unwanted matrix components and facilitate accurate analysis.

Step Ⅳ

Raw LC-MS/MS data collection and reduction: Raw data obtained from LC-MS/MS analyses are collected, including mass spectra, chromatograms, and other relevant information. Raw data is then processed and reduced to a manageable format for further analysis.

Advantages of Our Services

• Large-scale screening programs available
• High-throughput rapid screening to accommodate customers' manufacturing test cycles
• Flexibility to customize protocols according to customer needs
• Stroke drug candidates can be prioritized based on their ADME characteristics while optimizing their efficacy in the early detection phase.
• Combination of in vitro screening and computer simulation to help clients generate ADME data

Ace Therapeutics provides cost-effective HT-ADME screening and generates large amounts of standardized, high-quality data for predictive purposes to help clients accelerate stroke drug development. If you are interested in our services, please do not hesitate to contact us!

1. Shou, W. Z. (2020). Current status and future directions of high-throughput ADME screening in drug discovery. Journal of Pharmaceutical Analysis, 10(3), 201-208.