Integrating Pharmacokinetics and Quantitative Systems Pharmacology Approaches in Generative Drug Design.

ABSTRACT: Integrated understanding of pharmacokinetics (PK) and pharmacodynamics (PD) is a key aspect of successful drug discovery. Yet in generative computational drug design, the focus often lies on optimizing potency. Here we integrate PK property predictions in DrugEx, a generative drug design framework and we explore the generated compounds' PD through simulations with a quantitative systems pharmacology (QSP) model. Quantitative structure-property relationship models were developed to predict molecule PK (clearance, volume of distribution and unbound fraction) and affinity for the Adenosine A_2AR receptor (A_2AR), a drug target in immuno-oncology. These models were used to score compounds in a reinforcement learning framework to generate molecules with a specific PK profile

SUBMITTER: van den Maagdenberg HW 

PROVIDER: S-EPMC12117666 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature