Pendrin Corrector Compounds for Protein Folding and Membrane Rescue

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Solution Overview

Problem

Current pharmacological modulators are inadequate in addressing pendred syndrome and related diseases caused by pendrin defects, which affect ion transport and lead to auditory sensory transduction defects.

Innovation Solution

A novel compound represented by Chemical Formula 1, its optical isomers, precursors, pharmaceutically acceptable salts, and solvates, which act as a pendrin corrector to facilitate proper folding and functional expression of pendrin proteins on the cell membrane.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pharmacological modulators are used to rescue ion channel functions, then the function of membrane transporters can be restored, but existing modulators are inadequate for pendrin defects

Engineering Contradiction:

Improveefficacy of pendrin function rescueVSAvoidavailability of suitable modulators

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops novel chemical compounds with specific molecular structures (Formula 1 and Formula 2) that differ from existing modulators. These compounds contain specific functional groups and structural features designed to interact with pendrin, representing a parameter change in chemical structure to achieve the desired pharmacological effect for pendrin defects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces corrector compounds as intermediary substances that mediate between the defective pendrin protein and its proper function. These compounds act as pharmacological chaperones that bind to pendrin and facilitate its correct folding and trafficking to the cell membrane, serving as a mediator to restore ion transport function

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If correctors are used to help mutated polypeptides fold properly, then functional transporter proteins can be formed, but the compound must specifically target pendrin structure

Engineering Contradiction:

Improveproper folding of pendrin proteinVSAvoidspecificity of compound design

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent designs compounds with specific local structural features that target particular regions or conformational states of the pendrin protein. The molecular structures contain specific functional groups and spatial arrangements designed to interact with specific domains of pendrin, ensuring proper local folding while maintaining overall protein structure

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs specific molecular parameters including ring structures, substituent groups, and stereochemical configurations in the compound designs. These parameter changes in chemical structure are optimized to match the binding requirements of pendrin's folding intermediates, achieving high specificity for pendrin among membrane transporters

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250340537A1Pharmaceutically active compounds, compositions, and methods for modulating pendrin

Publication Date: 2025.11.06 ARBORMED CO LTD

AI summary

The present invention relates to a novel compound as pendrin corrector represented by the following Chemical formula 1 and a composition for preventing or treating pendred syndrome and the related disease thereof comprising the same as an active ingredient: