David S. Weinstein

The paper identifies covalent ligands targeting a cryptic cysteine in CRBN, demonstrating their ability to inhibit neosubstrate degradation by trapping CRBN in an inactive conformation.

This paper introduces VVD-065, a covalent NRF2 inhibitor that enhances NRF2 degradation and sensitizes tumors to therapy, supporting a Phase I clinical trial.

The paper develops covalent inhibitors targeting the RAS binding domain of PI3Kα, showing efficacy against RAS and HER2-driven tumors without affecting glucose homeostasis.