Targeted Protein Degraders: Through the Lens of the Innovation, Developability, and CMC Challenges
Summary: Developing Bifunctional TPDs with good oral bioavailability can be challenging, and a number of issues can arise throughout development. Understanding the molecular properties (such as polarity, flexibility and chameleonicity) of these complex molecules and their influence on solubility. In this article, experts review the trends and challenges associated with the rational design of targeted protein degrader drugs. In addition, experts also share perspectives on how to inform the selection and development of orally bioavailable drugs, and CMC approaches to efficiently develop and manufacture targeted protein degraders.