CFTR Modulators Restore Anion Transport in Cystic Fibrosis
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Solution Overview
Problem
Current treatments for cystic fibrosis and related diseases are inadequate due to the defective functioning of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, particularly the ΔF508 mutation, which impairs protein folding and trafficking, leading to reduced anion transport and severe clinical manifestations.
Innovation Solution
Development of compounds that modulate CFTR activity, specifically those with the general Formula (I), which can enhance or restore the function of wild-type and mutant CFTR forms, including ΔF508, to improve anion and bicarbonate transport across epithelial membranes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CFTR protein is defective due to mutations (particularly ΔF508), then protein folding and trafficking are impaired, but this leads to reduced anion transport and severe clinical manifestations
Solution Approach 1:
The patent introduces CFTR modulators as intermediary substances that bind to the CFTR protein and restore its function. These modulators act as mediators between the defective protein and the physiological system, correcting the harmful effects of mutation without requiring the protein to be fully functional in its wild-type state. The modulators specifically target and correct the folding and trafficking defects caused by mutations like ΔF508.
Solution Approach 2:
The patent employs chemical compounds that alter the functional parameters of CFTR protein through binding interactions. These modulators change the conformational state, trafficking efficiency, or channel activity of the protein, thereby restoring anion transport function. The chemical structure and binding characteristics of these modulators enable parameter changes that compensate for genetic defects.
2Productivity
If CFTR anion transport is reduced, then fluid transport is impaired, but this causes mucus accumulation and microbial infections
Solution Approach 1:
The patent aims to restore continuous and adequate anion transport through CFTR modulators, ensuring that the chloride channel function is maintained at physiological levels. By continuously activating the CFTR channel, the modulators prevent the accumulation of mucus that would otherwise result from intermittent or insufficient anion transport, thereby eliminating the harmful effect of mucus buildup.
3Ease of operation
If current treatments are used, then some symptom relief may be achieved, but the treatments are inadequate and do not fully restore CFTR function
Solution Approach 1:
The patent develops novel CFTR modulators that replicate and enhance the functional effects of existing treatments with improved efficacy. These new compounds are designed to more effectively restore CFTR function, providing a superior copy of the therapeutic action compared to current standard treatments, thereby achieving more reliable function restoration while maintaining ease of administration.
Data Source
AI summary
The present invention relates to modulators of cystic fibrosis transmembrane conductance regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using modulators of CFTR.