Ryanodine Receptor Modulators for Cardiac Arrhythmia Treatment
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Solution Overview
Problem
Current treatments for cardiac arrhythmias and heart failure often fail to effectively modulate the activity of calcium ion channels, particularly ryanodine receptors, leading to abnormal calcium release and increased risk of arrhythmias and heart failure.
Innovation Solution
Development of compounds that specifically target and modulate the activity of calcium ion channels, such as ryanodine receptors, to inhibit abnormal calcium release, thereby reducing the risk of arrhythmias and heart failure by altering the redox potential of reactive thiols on these channels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for cardiac arrhythmias and heart failure, then general cardiac support is provided, but effective modulation of calcium ion channel activity is not achieved
Solution Approach 1:
The patent applies parameter changes by modifying the redox state of reactive thiol groups on ryanodine receptors through administration of antioxidants or redox-modulating compounds. This changes the oxidation-reduction parameter of the channel proteins, thereby altering channel open probability and calcium release characteristics to treat arrhythmias and heart failure specifically.
2Reliability
If compounds target and modulate ryanodine receptor activity to inhibit abnormal calcium release, then arrhythmia risk is reduced, but normal systolic calcium release must not be interfered with
Solution Approach 1:
The patent applies local quality by selectively targeting the redox state of specific thiol groups on ryanodine receptors that are responsible for abnormal calcium release during diastole, while preserving the function of channels during systole. The compounds modify local chemical properties (redox state) at specific sites on the channel protein to achieve selective inhibition of pathological calcium leak without affecting physiological calcium release.
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
The compounds effectively inhibit abnormal calcium release, reducing the risk of arrhythmias and heart failure by targeting ryanodine receptors without interfering with normal systolic calcium release, thus providing a therapeutic benefit for conditions like CPVT and ventricular arrhythmias.
Implementation Method 1
altering the redox potential of reactive thiols on these channels
Data Source
AI summary
This disclosure concerns compounds and a method for modulating the activity of calcium ion channels, including Ca2+-induced (or Ca2+-activated) calcium release channels and conformationally coupled calcium release channels such as ryanodine receptors. Some of the compounds have a structure according to formula I, or a stereoisomer, tautomer, hydrate, solvate, prodrug, or pharmaceutically acceptable salt thereof.