Spirocyclic compounds as modulators of KRAS and uses thereof
Spirocyclic compounds targeting KRAS proteins' allosteric sites offer a solution to inhibit KRAS variants, effectively treating cancers by modulating their activity and regulating cellular proliferation.
WO2025194054A1 Publication Date: 2025-09-18AMGEN INC
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Patent Information
- Application Number
- PCT/US2025/019960
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-05-10
- Filing Date
- 2025-03-14
- Publication Date
- 2025-09-18
AI Technical Summary
Technical Problem
Existing inhibitors have struggled to target KRAS proteins, particularly KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, and G12C, due to the absence of druggable pockets on the protein surface, hindering effective treatment of cancers such as non-small cell lung cancer, colorectal cancer, pancreatic cancer, and others.
Method used
Development of spirocyclic compounds that act as inhibitors of KRAS proteins by binding to allosteric sites, including KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, or G12C, through specific structural modifications.
Benefits of technology
The spirocyclic compounds effectively inhibit KRAS proteins, providing therapeutic options for treating various cancers by modulating their activity and regulating cellular proliferation.
✦ Generated by Eureka AI based on patent content.
Abstract
Disclosed herein are compounds useful for the inhibition of KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C. The compounds have a general Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein the variables of Formula (I) are as defined herein. Also provided herein are pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a KRAS G12D, G12V, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R or G12C disorder.
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