addressing a major limitation in monotherapy PROTAC treatments known as the "hook effect"—the loss of degradation efficacy at high drug concentrations due to excessive binary complex formation.

Key findings presented include: VHL-based PROTACs targeting KRAS G12D display the classic hook effect at high concentrations; KEAP1-based PROTACs synergize with VHL-based PROTACs to enhance KRAS ...

The second presentation at AACR highlighted a novel bifunctional degrader strategy that combines two PROTACs using two E3s targeting KRAS G12D, addressing a major limitation in monotherapy PROTAC ...

“Combinatorial use of VHL and KEAP1-based PROTACs reveals unexpected synergy and hook effect relief,” related to the targeting of mutant KRAS G12D as well as other oncogenes. “Our team’s research ...