Small-Molecule UBR-Box Ligands for N-End Rule Pathway Modulation

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Solution Overview

Problem

Existing technologies lack effective ligands that can bind to the UBR box domain, which is crucial for regulating intracellular proteolytic pathways, leading to unaddressed issues in diseases related to excessive protein degradation.

Innovation Solution

Development of small molecule compounds that specifically bind to the UBR box domain, inhibiting substrate binding and thereby modulating the N-end rule pathway to treat UBR-related diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If no ligand is developed for UBR box domain, then the N-end rule pathway continues to degrade proteins unchecked, but no therapeutic intervention is available for UBR-related diseases

Engineering Contradiction:
Improvetherapeutic intervention availabilityVSAvoidpathway regulation capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces small molecule compounds as intermediary substances that bind to the UBR box domain to modulate its activity. These compounds act as mediators between the therapeutic need and the biological pathway, allowing external control of the N-end rule pathway without directly altering the pathway's genetic or enzymatic components.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If existing technologies are used without specific UBR box domain ligands, then general protein degradation pathways remain active, but specific modulation of the N-end rule pathway is impossible

Engineering Contradiction:
Improvepathway modulation capabilityVSAvoidligand development requirement
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs small molecule compounds that induce parameter changes in the UBR box domain's binding characteristics. By introducing molecules with specific chemical structures and properties, the pathway's substrate binding parameters are modified, enabling selective modulation of protein degradation without changing the underlying genetic or enzymatic parameters of the system.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP4144720B1Compound as UBR-box domain ligand
Publication Date: 2025.08.27 AUTOTAC
  • EP4144720B1 patent drawingFigure 1
  • EP4144720B1 patent drawingFigure 2
  • EP4144720B1 patent drawingFigure 3

AI summary

The present specification relates to a compound as a UBR box domain ligand. The present specification provides a small molecule compound that binds to the UBR box domain. Further, the present specification provides a composition for inhibiting UBR box domain substrate binding, including a ligand compound that binds to a UBR box domain, a pharmaceutical composition for treating UBR-related disease, and a use thereof.