KEAP1 Inhibitors Modulate Nrf2 Pathway for Oxidative Stress

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Solution Overview

Problem

Current therapeutics are inadequate for effectively treating immunological disorders such as inflammatory bowel disease, Crohn's disease, and ulcerative colitis, as they do not adequately address oxidative stress and inflammation.

Innovation Solution

Development of compounds that modulate KEAP1 to indirectly activate Nrf2 by inhibiting its degradation, thereby increasing antioxidant capacity and reducing oxidative stress in cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapeutics are used for immunological disorders, then treatment is provided, but oxidative stress and inflammation are not adequately addressed

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidoxidative stress

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the biochemical parameter of cellular redox state by introducing compounds that modify KEAP1 function, thereby altering Nrf2 degradation rates and increasing antioxidant enzyme expression to counteract oxidative stress in immunological disorders

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses KEAP1 as an intermediary target - by modulating KEAP1 activity with specific compounds, the pathway leading to Nrf2 degradation is controlled, which in turn regulates the expression of cytoprotective enzymes that address oxidative stress without directly targeting the stress itself

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If Nrf2 degradation is inhibited by KEAP1 antagonists, then antioxidant capacity increases, but the mechanism requires indirect activation through protein-protein interaction modulation

Engineering Contradiction:

Improveantioxidant defenseVSAvoidmechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent enables the cell's own antioxidant defense system to be activated by small molecules that modulate KEAP1-Nrf2 interaction, allowing the endogenous Nrf2-ARE pathway to self-regulate and upregulate protective enzymes without requiring external direct activation of Nrf2

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent changes the interaction parameter between KEAP1 and Nrf2 proteins by introducing compounds that bind to KEAP1 and alter its ability to promote Nrf2 degradation, thereby shifting the equilibrium toward increased Nrf2 stability and activity

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250011291A1KEAP1 inhibitors and uses thereof

Publication Date: 2025.01.09 VIVIDION THERAPEUTICS INC

AI summary

Compounds and methods for activating Nrf2 by inhibiting KEAP1.