NLRP3 Inflammasome Modulators With Reduced Cardiotoxicity
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Solution Overview
Problem
Existing treatments for diseases associated with NLRP3 inflammasome dysregulation, such as neuroinflammation and neurodegenerative disorders, are inefficient and pose risks of cardiotoxicity, highlighting the need for modulators that can inhibit the NLRP3 inflammasome without causing substantial toxicity.
Innovation Solution
Development of compounds that interact with the NLRP3 inflammasome to block its ATPase function, inhibiting its activation and downstream cytokine release, thereby reducing inflammation and cell death while minimizing cardiotoxicity risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used to inhibit NLRP3 inflammasome, then inflammatory diseases may be treated, but cardiotoxicity risk increases
Solution Approach 1:
The patent modifies the chemical structure of existing NLRP3 modulators by changing molecular parameters (substituents, ring systems, functional groups) to improve the therapeutic index. Specifically, the compounds in Formula I represent a series of structurally modified molecules designed to maintain NLRP3 inhibition while reducing cardiotoxic effects through optimized molecular properties
Solution Approach 2:
The patent introduces new compound structures as intermediary substances that mediate between the desire to inhibit NLRP3 inflammasome and the need to avoid cardiotoxicity. These compounds act as selective modulators that target NLRP3 with higher specificity and reduced off-target effects compared to existing treatments
2Reliability
If NLRP3 inflammasome is activated to fight infection, then immune response is enhanced, but inflammation and tissue damage increase
Solution Approach 1:
The patent develops dynamic modulators that can regulate NLRP3 inflammasome activity in a controlled manner. The compounds provide reversible and tunable inhibition, allowing the system to maintain immune defense capabilities while preventing excessive inflammation. This dynamic control enables the body to respond appropriately to threats without suffering from uncontrolled inflammatory damage
Data Source
AI summary
Compounds are provided for inhibiting NLRP3 inflammasome generally, or for treating a NLRP3 inflammasome dependent condition more specifically, by contacting the NLRP3 inflammasome or administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein A, B, X1, R1, R2, R3, m, n, and p are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.