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CRBN-based pan-KRAS degrader
- Development stage
- Preclinical
- Lead developer
- University of Michigan
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
- Administration
- Intraperitoneal, Subcutaneous, Intravenous, Oral, Intramuscular, Transdermal
01
Overview
A CRBN-based pan-KRAS proteolysis-targeting chimera (PROTAC) developed by researchers at the University of Michigan, led by Shaomeng Wang. This therapeutic agent is designed to induce the degradation of multiple oncogenic KRAS mutants, including G12D, G12V, and G12C, by recruiting the Cereblon (CRBN) E3 ubiquitin ligase. By eliminating the KRAS protein rather than merely inhibiting its activity, this degrader aims to overcome the rapid onset of resistance typically seen with traditional KRAS inhibitors and disrupt the protein's scaffolding functions. Preclinical data presented at AACR 2026 demonstrated sub-nanomolar potency in vitro and significant tumor regression (over 90%) in xenograft models of colorectal and pancreatic cancers with once-weekly dosing.
- Other names
- pan-KRAS PROTACCRBN-based KRAS degrader
02
Targets
CRBN (Cereblon)KRAS (Kirsten rat sarcoma viral oncogene homolog)
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