Proximity-First: A Multi-Tiered Molecular Glue Discovery Cascade for Undruggable Targets

• Anchoring hit identification on a highly sensitive, gain-of-signal biochemical proximity assay to maximize early detection of ternary-complex formation, opening a productive front-line screen for undruggable targets defined by weak or transient basal target and ligase interactions

• Sequencing a tiered validation cascade, spanning biochemical proximity, binder competition, functional ubiquitination, and cellular degradation, in which each tier enforces a distinct mechanistic criterion that systematically eliminates proximity-only false positives before committing chemistry resources

• Translating this orthogonally cross-validated funnel into confident go/no-go decisions and a generalizable, plug-and-play discovery framework that is portable across diverse undruggable targets and E3 ligases

Speakers:

Ajinkya Patil

Principal Scientist

Pfizer