In silico ADME-Tox modeling: progress and prospects.

Area of Science:

• Pharmacology
• Computational Chemistry
• Drug Development

Background:

• In silico models are vital for predicting Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADME-Tox) properties in drug discovery.
• Despite advancements in high-throughput screening, computational ADME-Tox prediction remains essential for selecting viable drug candidates early in development.
• This review focuses on the utility of in silico models in drug discovery and development.

Purpose of the Study:

• To provide an overview of in silico models used for predicting ADME-Tox properties.
• To summarize the latest modeling methods and algorithms for predicting physicochemical characteristics, ADME properties, and drug toxicity.
• To highlight the role of these models in facilitating candidate drug selection.

Main Methods:

• Review of existing literature on in silico ADME-Tox prediction models.
• Summarization of current modeling techniques and algorithms.
• Discussion of Physiologically Based Pharmacokinetic (PBPK) models as a comprehensive approach.

Main Results:

• In silico models have significantly advanced early-stage drug discovery screening.
• A wide range of models exist for predicting various ADME-Tox parameters.
• PBPK models offer a pathway to predict in vivo pharmacokinetics and compound disposition.

Conclusions:

• Current in silico models are valuable tools in drug discovery and development.
• PBPK models represent a promising approach for integrated pharmacokinetic prediction.
• Further data generation and parameter refinement are necessary to enhance the reliability and accuracy of in silico prediction models.