CFTR Modulator Composition for Trafficking and Channel Gating Defects
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Solution Overview
Problem
Current treatments for cystic fibrosis (CF) are inadequate, as mutations in the CFTR protein lead to reduced anion transport, causing mucus accumulation and microbial infections, with no cure available, and affect gastrointestinal function and fertility.
Innovation Solution
Development of compounds such as N-(benzenesulfonyl)-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]-2-[(4(S))-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide (Compound I) and related CFTR modulators that act as correctors and potentiators to enhance CFTR activity, correcting trafficking defects and increasing channel function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for cystic fibrosis, then current standard care is provided, but anion transport remains reduced and mucus accumulation continues
Solution Approach 1:
The patent applies parameter changes by administering CFTR modulators (correctors and potentiators) that alter the functional parameters of the CFTR protein. Correctors change the trafficking parameter to enable proper membrane localization, while potentiators change the gating parameter to increase channel open probability, thereby restoring anion transport function and reducing mucus accumulation
Solution Approach 2:
The patent uses CFTR modulators as intermediary substances that mediate between the defective CFTR protein and normal physiological function. These small molecule compounds bind to the CFTR protein and act as intermediaries to correct folding/trafficking defects and enhance channel activity, translating the defective protein into a functional state
2Reliability
If CFTR modulators are administered, then anion transport is enhanced, but the complexity of treatment regimens increases
Solution Approach 1:
The patent merges multiple therapeutic functions into a combination treatment regimen that administers both corrector and potentiator compounds. This combination approach consolidates the effects of correcting trafficking defects and enhancing channel gating into a unified treatment strategy, achieving synergistic restoration of CFTR function while managing the complexity through standardized dosing protocols
Data Source
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AI summary
Compound I of the formula (formula) A pharmaceutically acceptable salt of Compound I. Pharmaceutical compositions containing at least Compound I and methods of treating cystic fibrosis comprising administering at least Compound I. Pharmaceutical compositions containing a pharmaceutically acceptable salt of at least Compound I and methods of treating cystic fibrosis comprising administering a pharmaceutically acceptable salt of at least Compound I.