Heterocyclic STING Modulators for Tunable Interferon Signaling
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Solution Overview
Problem
Current therapies for modulating the STING pathway are limited in their ability to effectively treat a wide range of diseases, including inflammatory, allergic, autoimmune, infectious, and cancerous conditions, as well as providing vaccine adjuvancy, due to the specificity and efficacy challenges of existing compounds.
Innovation Solution
Development of benzothiophene, thienopyridine, and thienopyrimidine derivatives that can modulate the activity of STING, acting as either agonists or antagonists to induce or inhibit type I interferon production, thereby addressing various disease pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing STING pathway modulating compounds are used, then specific disease treatment is achieved, but the ability to effectively treat a wide range of diseases is limited
Solution Approach 1:
The patent applies universality by designing a broad class of STING modulating compounds that can treat multiple disease types (inflammatory, allergic, autoimmune, infectious, and cancerous conditions) through a single structural framework. The invention identifies common molecular features across different disease states and creates compounds that can modulate STING pathway activity to address diverse pathologies, thereby achieving multi-functionality without sacrificing specificity for individual disease treatments.
2Reliability
If STING pathway is activated to treat infectious diseases, then immune response is enhanced, but excessive activation may lead to autoimmune conditions
Solution Approach 1:
The patent applies dynamics by creating STING modulating compounds that can be selectively activated or deactivated based on disease state requirements. The invention designs molecules with controllable binding affinity and signaling strength, allowing dynamic adjustment of STING pathway activation levels. This enables enhanced immune response for infectious diseases while preventing excessive activation that could lead to autoimmune conditions, through mechanisms that allow fine-tuned control of pathway activity.
Solution Approach 2:
The patent applies parameter changes by modifying molecular parameters of STING modulating compounds to achieve different levels and durations of pathway activation. The invention varies parameters such as binding affinity, half-life, and signaling strength to create compounds that provide sufficient immune activation for infection treatment while avoiding excessive activation. This allows precise control over the intensity and duration of STING pathway modulation to balance therapeutic benefit against harmful effects.
Data Source
AI summary
A compound of formula (I): wherein: Y is (CH2)n, where n is from 2 to 4; W1 and W11 are independently selected from OH and ORP, where RP is Me or Et.