Structure-ADME relationship: still a long way to go?

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Computational Chemistry
• Drug Discovery and Development

Background:

• In silico models are crucial for predicting Absorption, Distribution, Metabolism, and Excretion (ADME) properties.
• These predictions support the drug development pipeline.

Purpose of the Study:

• To review in silico prediction models for key ADME properties: aqueous solubility, human intestinal absorption, and oral bioavailability.
• To focus on the predictive accuracy of these computational models.

Main Methods:

• Review of existing in silico models for ADME property prediction.
• Analysis of prediction accuracies rather than detailed model descriptions.

Main Results:

• Prediction accuracy is linked to the complexity of the ADME property.
• In silico models struggle with complex phenomena like bioavailability.
• Limited large, high-quality datasets hinder ADME prediction reliability.

Conclusions:

• Significant progress in ADME prediction, but challenges persist.
• Model complexity and data availability are key limitations.
• Further research is needed to improve the reliability of in silico ADME predictions.