Targeted protein degradation (TPD) technologies, exemplified by PROTAC and molecular glue, represent a revolutionary drug discovery paradigm that operate through an "event-driven" mechanism. These technologies are widely utilized in chemical biology research and drug discovery, successfully advancing over 50 innovative drugs into Phase 1–3 clinical trials. However, critical challenges persist in the TPD field, including inability of targeting "unligandable" proteins, overreliance on CRBN- and VHL-based E3 ligase ligands, narrow therapeutic focus predominantly in oncology, and difficulty of achieving tissue-selective degradation of targeted protein, which collectively hinder the further development of TPD field.

    Our group aims to overcome these critical bottlenecks by developing next-generation TPD therapeutics, expanding their target/indication scope, and pioneering spatiotemporal-selective degradation strategies. Specific research directions include:

    (1) Rational discovery and mechanistic studies of molecular glue degraders targeting "unligandable" transcription factors.

    (2) Discovery of small molecule ligands for underexplored E3 ligases to expand the E3 ligase toolbox beyond CRBN/VHL.

    (3) Discovery and development of targeted protein degraders for the treatment of inflammatory diseases and neurodegenerative diseases.

    (4) Discovery of small molecular degraders with spatiotemporal selectivity.