Quinoline Derivatives Modulating SERCA for ER Stress
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Solution Overview
Problem
Current therapies lack effective solutions for reducing endoplasmic reticulum stress, which is linked to various diseases such as diabetes, neurodegenerative disorders, and cancer, and for modulating the activity of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) to restore cellular homeostasis.
Innovation Solution
Administration of a compound of Formula I, or its enantiomers, diastereomers, or isotopic variants, or their pharmaceutically acceptable salts, solvates, or prodrugs, which are quinoline derivatives, to treat or prevent symptoms of endoplasmic reticulum stress-related diseases by reducing stress and modulating SERCA activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used, then treatment of various diseases can be provided, but effective reduction of endoplasmic reticulum stress and modulation of SERCA activity cannot be achieved
Solution Approach 1:
The patent employs parameter changes by developing a series of quinoline derivative compounds with varying chemical structures (Formula I with different R1, R2, R3, R4, R5, R6, R7, R8 substituents) to optimize their ability to reduce ER stress and modulate SERCA activity. This systematic variation of molecular parameters allows the compounds to effectively address diseases linked to ER stress while providing the specific therapeutic action that current therapies lack.
2Stability of the object's composition
If ER stress is reduced and SERCA activity is modulated, then cellular homeostasis can be restored, but specific therapeutic agents capable of achieving this were previously unavailable
Solution Approach 1:
The patent applies segmentation by dividing the therapeutic approach into specific quinoline derivative compounds with defined chemical structures (Formula I). These segmented molecular entities can be individually synthesized, characterized, and optimized for reducing ER stress and modulating SERCA activity, making the therapeutic agent accessible and manufacturable while achieving the desired restoration of cellular homeostasis.
Data Source
AI summary
Provided herein are quinoline, pharmaceutical compositions thereof, and methods of their use for treating, preventing, or ameliorating one or more symptoms of an endoplasmic reticulum stress-caused disease. Also provided herein are methods of their use for reducing endoplasmic reticulum stress and modulating the activity of a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase.