Department of Chemistry Seminar - Targeted Degradation of Intra- and Extracellular Proteins: A Chemistry-Driven Approach to Advancing Translational Research

Speaker: Prof. Weiping TANG

Institution: School of Pharmacy, University of Wisconsin–Madison, USA

Hosted by: Prof. Yong HUANG

Abstract

In recent years, the Tang laboratory has focused on developing chemistry-based enabling platforms—novel strategies, tools, and modalities designed to accelerate translational research in the area of targeted protein degradation, including proteolysis-targeting chimeras (PROTACs), molecular glue degraders (MGDs), and lysosome-targeting chimeras (LYTACs) for the selective degradation of intra- and extracellular disease-associated proteins. For PROTACs and MGDs, we have developed two streamlined platforms, Rapid-TAC and Rapid-Glue, to facilitate the generation of large degrader libraries suitable for direct biological screening. These approaches accelerate the exploration of chemical space and enable the rapid identification of potent intracellular protein degraders. In the area of LYTACs, we have explored diverse lysosome-targeting receptors to engineer tissue-selective degraders with demonstrated efficacy both in vitro and in vivo. By integrating receptor biology with rational chemical design, we aim to expand the therapeutic potential of LYTACs and achieve precise extracellular protein degradation in a tissue-selective manner. Together, these platforms provide powerful tools for advancing targeted protein degradation across diverse biological systems and therapeutic applications. The underlying design principles may also have broader applications in the emerging field of induced proximity, opening new opportunities for therapeutic discovery and development.