eIF2B-Activating Compound for Integrated Stress Response Modulation

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Solution Overview

Problem

There is no effective treatment for Amyotrophic Lateral Sclerosis (ALS) that can stop or reverse the progression of the disease, and existing treatments targeting the integrated stress response (ISR) have limitations in managing neurodegenerative diseases.

Innovation Solution

A compound is developed to significantly reduce the integrated stress response (ISR) and activate the activity of eIF2B, promoting normal protein synthesis in cells, which can be used in pharmaceutical compositions to treat diseases related to eIF2B regulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies targeting the integrated stress response (ISR) are used, then some treatment effect is achieved, but they have limitations in managing neurodegenerative diseases and cannot stop or reverse disease progression

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidability to stop or reverse disease progression

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the chemical structure of known eIF2B activators by introducing specific substituents and functional groups to create compound (1), which demonstrates enhanced pharmacological properties including improved ability to activate eIF2B and reduce ISR, potentially overcoming the limitations of existing therapies

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent combines multiple pharmacophore elements and functional groups into a single molecular structure that integrates the key features of known eIF2B activators with additional moieties that enhance efficacy and address the shortcomings of current treatments

Inventive Principle:

Principle #40Composite materials

2Stability of the object's composition

If the integrated stress response (ISR) is activated to restore protein homeostasis, then protein folding balance is maintained, but long-term memory formation is inhibited and cognitive function deteriorates

Engineering Contradiction:

Improveprotein homeostasisVSAvoidcognitive function and memory formation

Core Design Contradiction:

Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent aims to partially activate eIF2B to achieve sufficient reduction of ISR pathways to improve cognitive function, while avoiding complete suppression that would compromise protein homeostasis, thus finding an optimal balance point

Inventive Principle:

Principle #16Partial or excessive action

Solution Approach 2:

The compound acts as an intermediary that modulates the ISR pathway by activating eIF2B, thereby indirectly regulating both protein homeostasis and cognitive function without directly interfering with either process

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS12612392B2Compound, pharmaceutical compositions containing same, synthesis method therefor and use thereof

Publication Date: 2026.04.28 SHENZHEN ZHONGGE BIOLOGICAL TECH CO LTD

AI summary

The present application provides a compound as shown in formula (0), a pharmaceutical composition containing same, a synthesis method therefore and a use thereof. The compound of the present application can significantly reduce the integrated stress response (ISR) of cells and activate the activity of eIF2B, so that the protein in the cells tends to be synthesized normally, providing more possible drugs for ISR pathway-mediated diseases or condition eIF2B-related diseases, and/or diseases related to regulation of the activity or level of eIF2B activity or level, and regulation of the activity or level of the eIF2 pathway or ISR pathway.