CFTR Modulator Compounds for Cystic Fibrosis Treatment
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Solution Overview
Problem
Current treatments for cystic fibrosis and related diseases, such as asthma and COPD, are limited in effectively modulating the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is crucial for ion and fluid transport across epithelial cells, leading to impaired mucus clearance and respiratory issues.
Innovation Solution
Development of compounds that modulate the activity of CFTR by interacting with its binding domains, specifically targeting the ABC transporter proteins to enhance or reduce anion secretion, thereby treating a range of diseases associated with defective CFTR function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used to modulate CFTR activity, then some therapeutic effect is achieved, but the treatment is limited in effectiveness and scope
Solution Approach 1:
The patent provides a broad class of compounds that can modulate CFTR activity across multiple disease states (cystic fibrosis, asthma, COPD, pancreatitis, infertility) through a single unified chemical structure. This allows one treatment approach to address multiple conditions caused by CFTR dysfunction, expanding therapeutic scope while maintaining effectiveness.
Solution Approach 2:
The invention utilizes structural parameter changes in the chemical compounds (varying R1-R6 groups, aromatic rings, heteroatoms) to optimize CFTR modulation. By adjusting these molecular parameters, the compounds can effectively target different CFTR mutations and disease states, enhancing therapeutic reliability across diverse conditions.
2Productivity
If CFTR activity is enhanced to improve ion and fluid transport, then mucus clearance improves, but the complexity of treating multiple disease states increases
Solution Approach 1:
A single class of compounds can address multiple disease states (respiratory, gastrointestinal, reproductive) through CFTR modulation, eliminating the need for separate treatment regimens for each condition. This reduces treatment complexity while maintaining high mucus clearance effectiveness across all affected organs.
Solution Approach 2:
The patent segments the treatment approach by providing specific compound examples (formula I and II) that can be selectively used for different disease states, allowing clinicians to simplify treatment by choosing from a standardized set of compounds rather than developing custom regimens for each condition.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds effectively treat or lessen the severity of cystic fibrosis, asthma, COPD, and other diseases by improving CFTR activity, leading to enhanced ion and fluid transport, improved mucus clearance, and reduced respiratory symptoms.
Implementation Method 1
compounds that modulate the activity of CFTR by interacting with its binding domains, specifically targeting the ABC transporter proteins
Implementation Method 2
ATP cassette transporters are a family of membrane transporter proteins that regulate the transport of a wide variety of pharmacological agents, potentially toxic drugs, and xenobiotics, as well as anions. They are homologous membrane proteins that bind and use cellular adenosine triphosphate (ATP) for their specific activities.
Data Source
AI summary
The present invention relates to compounds of formula IVA, formula IVB, or formula IVC, useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating diseases using such CFTR modulators.