Heterobifunctional compounds for the degradation of KRAS protein
Heterobifunctional compounds targeting KRAS via the ubiquitin proteasome pathway address the challenge of KRAS resistance by degrading KRAS mutants, offering prolonged therapeutic effects and increased potency.
WO2026139448A1PCT designated stage Publication Date: 2026-07-02MERCK PATENT GMBH
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Patent Information
- Application Number
- PCT/EP2025/088661
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-12-23
- Filing Date
- 2025-12-22
- Publication Date
- 2026-07-02
AI Technical Summary
Technical Problem
Current KRAS targeting agents are challenging to develop due to KRAS's undruggable nature, and resistance often develops quickly, limiting their effectiveness in treating KRAS-mediated cancers.
Method used
Development of heterobifunctional compounds that degrade KRAS protein via the ubiquitin proteasome pathway, specifically targeting mutations like G12D, G12C, G12V, and G13D, using formulas I, Ia, and III to selectively target and degrade KRAS mutants.
Benefits of technology
These compounds effectively degrade KRAS mutants, overcoming resistance and providing prolonged therapeutic effects by destroying the protein, thus requiring resynthesis, and potentially offering increased potency and broader targeting compared to traditional inhibitors.
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Abstract
The invention provides compounds that degrade the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein including mutant forms via the ubiquitination of the KRAS protein and subsequent proteasomal degradation. The compounds are useful for the treatment of various cancers.
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