CFTR Modulator Compositions for Mutation Response and Tolerability
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Solution Overview
Problem
Current treatments for cystic fibrosis, such as lumacaftor and tezacaftor, do not effectively address all CFTR mutations and can cause side effects, necessitating the development of alternative therapeutic strategies to manage CFTR-related diseases and respiratory distress.
Innovation Solution
Development of CFTR modulators, including compounds like 3-(2,3-dichlorophenyl)-6-(tert-pentyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and N-(2-(cyclobutanecarboxamido)benzo[d]thiazol-6-yl)-1,3-dimethyl-1H-pyrazole-4-carboxamide, which enhance CFTR activity and are administered in combination with other agents to treat CFTR mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If lumacaftor and tezacaftor are used to treat CFTR mutations, then processing abnormalities associated with F508del mutation are overcome, but side effects occur that limit long term treatment tolerance
Solution Approach 1:
The patent introduces a new chemical compound as an intermediary substance that mediates the treatment of CFTR mutations. This compound, with specific chemical structure features (including heterocyclic rings and functional groups), acts as a molecular mediator to correct CFTR protein folding and processing abnormalities, thereby treating the underlying cause while potentially reducing side effects associated with existing therapies
Solution Approach 2:
The patent applies parameter changes by modifying chemical parameters (molecular structure, functional groups, heterocyclic ring configurations) to create a new therapeutic agent. By changing the chemical parameters of the treatment compound, the patent aims to achieve effective CFTR modulation while altering the side effect profile compared to existing drugs like lumacaftor and tezacaftor
2Reliability
If triple combination therapies are used, then benefits are shown in clinical testing, but some individuals do not respond to these therapies
Solution Approach 1:
The patent develops a compound with multi-functional capabilities to address different CFTR mutation types. The chemical structure is designed to potentially interact with various mutant CFTR proteins (including but not limited to F508del), making the treatment more universally applicable across different genetic variants and reducing response variability among patients
Solution Approach 2:
Instead of combining multiple existing drugs (triple combination therapy), the patent inverts the approach by developing a single new compound that aims to achieve the therapeutic effects of combination therapy. This single agent may address multiple aspects of CFTR dysfunction simultaneously, potentially improving response rates across diverse patient populations
3Reliability
If existing CFTR modulators are administered, then CFTR activity is enhanced, but the ability to tolerate long term treatment is limited
Solution Approach 1:
The patent develops a new chemical compound that may offer improved safety and tolerability for long-term use. By creating a disposable-like treatment approach with a novel chemical structure, the patent aims to provide effective CFTR modulation that can be administered over extended periods without the cumulative toxicity or side effects that limit current therapies
Solution Approach 2:
The compound is designed to self-regulate its interaction with CFTR protein, potentially achieving sustained therapeutic effects with appropriate dosing. The chemical structure includes features that may allow the compound to maintain stable binding and modulation of CFTR activity over time, supporting long-term treatment tolerance
Data Source
AI summary
This disclosure relates to compounds that are cystic fibrosis transmembrane conductance regulator (CFTR) modulators and pharmaceutical compositions containing the same. In certain embodiments, this disclosure relates to methods of managing a CFTR related disease or condition or respiratory distress comprising administering an effective amount of a CFTR modulator disclosed herein to a subject in need thereof.