Methods and compositions for treating cancers with high levels of microsatellite instability

CN122374028APending Publication Date: 2026-07-10EIKON THERAPEUTICS INC
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
EIKON THERAPEUTICS INC
Filing Date
2024-11-14
Publication Date
2026-07-10

AI Technical Summary

Technical Problem

The mechanisms by which WRN spatiotemporal dynamics in cells are not yet clear in existing technologies, resulting in limited therapeutic effects on cancers with high microsatellite instability (MSI-H).

Method used

By applying a combination of target protein degraders (TPDs) that target WRN, the activity of WRN can be modulated, including targeted degradation, promotion of association with chromatin, and alteration of WRN localization in cells. The therapeutic effect on MSI-H cancer can be enhanced by using target protein degraders (TPDs) such as PROTAC, deubiquitinase inhibitors, molecular glues, and degrader-antibody complexes.

Benefits of technology

It significantly reduces protein motility of WRN, promotes its localization from the nucleolus to chromatin, and enhances the therapeutic effect on MSI-H cancers, including colorectal cancer, gastric cancer, bladder cancer and other cancers.

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Abstract

This disclosure relates to methods and compositions for treating cancer (e.g., cancers containing MSI-H cells) by: targeting WRN for degradation (in the presence or absence of a WRN inhibitor); promoting WRN association with chromatin (in the presence or absence of a WRN inhibitor); and / or promoting WRN localization from the nucleolus to foci on the chromatin.
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