AAPS Webinar: DMPK Strategies for Proteolysis-Targeting Chimeras: Addressing ADME and PK Challenges

Webinar Overview:

The advancement of ARV-471 to NDA stage, together with multiple PROTAC^* candidates currently in clinical development, represents a transformative milestone in targeted protein degradation therapeutics. This collective progress validates the clinical translation of PROTAC technology and establishes critical benchmarks for addressing previously undruggable targets through induced protein degradation.

The DMPK characterization of PROTACs presents unique challenges due to their distinctive physicochemical properties and complex pharmacokinetic behavior. Their bifunctional architecture typically results in molecular weights exceeding 700 Da,  creating significant solubility and permeability barriers. The ternary complex formation mechanism leads to complex in vivo distribution patterns, while linker chemistry can introduce metabolic liabilities, making biotransformation pathways difficult to predict.

This program provides practical guidance for selecting optimal in vitro systems to evaluate PROTAC-specific ADME properties, covering advanced assays for solubility, permeability, protein binding, and biotransformation pathway elucidation, and further examines solutions to enhance PROTAC bioavailability through innovative formulation approaches, supported by case studies. Participants will gain expertise in designing and interpreting in vivo PK studies. The program also covers bioanalytical approaches and advanced  techniques for PROTAC quantification.

Designed for DMPK scientists and drug developers, this program delivers actionable insights of DMPK strategies to accelerate PROTAC therapeutics from discovery through clinical development.

*In this webinar, PROTAC specifically refers to the abbreviation of Proteolysis-Targeting Chimera as therapeutic modalities.