p53 HETEROBIFUNCTIONAL CONJUGATES AND USES THEREOF

Heterobifunctional molecules targeting p53 Y220C mutant proteins restore normal p53 activity, inducing cell cycle arrest and apoptosis in cancer cells, addressing the limitations of existing cancer treatments.

WO2026107406A1PCT designated stage Publication Date: 2026-05-21DESIGN THERAPEUTICS INC
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
DESIGN THERAPEUTICS INC
Filing Date
2025-11-14
Publication Date
2026-05-21

AI Technical Summary

Technical Problem

Current treatments for cancer, particularly those targeting mutated p53 proteins, are ineffective in restoring normal p53 activity and do not adequately address the transcriptional dysregulation caused by these mutations.

Method used

Development of heterobifunctional molecules that noncovalently bind to p53 Y220C mutant proteins, incorporating a p53-binding moiety and a protein-binding moiety linked by a specific structure, capable of reversing or promoting the transcriptional activity of p53 Y220C through interaction with endogenous regulatory proteins.

Benefits of technology

These molecules effectively reinstate normal p53 activity, leading to cell cycle arrest and apoptosis in cancer cells with mutated p53, while sparing wild-type p53 cells, thus providing a targeted therapeutic approach.

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Abstract

The present technology relates generally to compounds including a first terminus comprising a p53-binding moiety capable of noncovalently binding to p53 Y220C mutant protein; a second terminus comprising a protein-binding moiety capable of binding to an endogenous regulatory protein, wherein the endogenous regulatory protein reverses or promotes transcriptional activity of p53 Y220C; and a linker between the first terminus and the second terminus.
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