NLRP1 NLRP3 Inhibitor Compounds for Inflammasome Modulation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for conditions associated with aberrant activation of NLRP1 and NLRP3 inflammasomes are inadequate, as these inflammasomes are implicated in various complex diseases with no effective modulators available to inhibit their activity effectively.
Innovation Solution
Development of chemical entities that modulate NLRP1 and NLRP3 activity by antagonizing them, either by directly binding or inactivating these inflammasomes, thereby inhibiting the production of IL-10 and IL-18, which are administered as pharmaceutical compositions to treat diseases where NLRP1/3 signaling contributes to pathology.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for conditions associated with NLRP1 and NLRP3 inflammasomes, then existing therapeutic options are maintained, but effective inhibition of NLRP1/3 activity is not achieved
Solution Approach 1:
The patent employs parameter changes by systematically varying chemical structures (Formula I with multiple substitutable positions R1-R6, R7-R12, and ring systems) to optimize NLRP1/3 inhibition. This involves changing molecular parameters such as substituent types, ring sizes, and stereochemistry to achieve effective modulator activity where none previously existed.
Solution Approach 2:
The patent creates composite chemical entities by combining multiple structural components (heterocyclic rings, substituent groups, and linker moieties) into complex molecular architectures (Formula I and Formula II compounds). These composite structures work synergistically to achieve effective NLRP1/3 inhibition, representing a composite approach to drug design.
2Object-affected harmful factors
If NLRP1 and NLRP3 inflammasome activity is not inhibited, then existing therapeutic approaches continue, but pathology and symptoms in NLRP1/3-associated diseases progress
Solution Approach 1:
The patent applies preliminary anti-action by designing compounds that proactively inhibit NLRP1/3 inflammasome activation before pathological processes fully develop. The compounds prevent the formation of the inflammasome complex and subsequent IL-1β and IL-18 production, thereby preventing disease progression in conditions like CAPS, gout, and autoimmune diseases before symptoms worsen.
Solution Approach 2:
The patent converts the harmful overactive inflammasome response into a beneficial therapeutic outcome by using small molecule inhibitors to block the pathological NLRP1/3 signaling. The harmful inflammatory response is transformed into a controlled state where disease progression is halted, turning the pathological process into an opportunity for targeted intervention.
3Reliability
If effective NLRP1/3 modulators are developed, then disease treatment efficacy is improved, but complexity of compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the complex NLRP1/3 binding interface into discrete molecular components represented by Formula I and Formula II structures. Each compound is segmented into functional modules (core ring system, substituent groups, and linker regions) that can be independently optimized, allowing complex therapeutic activity to be achieved through modular assembly rather than monolithic complexity.
Data Source
AI summary
In one aspect, compounds of Formulae (I) and (II), or pharmaceutically acceptable salts thereof, are featured; Formula (I), Formula (II) or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formulae (I) and (II) can be as defined anywhere herein.