STING Activator Compounds Optimizing Binding Affinity and Oral Bioavailability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for compounds that can bind to and activate STING, a critical signaling molecule in the innate immune system, to stimulate type 1 interferons and cytokines, which are essential for treating inflammatory diseases, autoimmune diseases, infectious diseases, and cancer, while also being orally bioavailable and having appropriate pharmacokinetic properties.
Innovation Solution
Development of novel compounds of specific formulae that bind to STING, activate it, and induce type 1 interferons and cytokines, which are administered as pharmaceutical compositions to treat various diseases and serve as vaccine adjuvants, with methods for their preparation and use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule compounds are designed to bind to and activate STING, then immune response stimulation is improved, but oral bioavailability and pharmacokinetic properties may be compromised
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structures (formulae A, I, II, III, IV, V, VI, VII, VIII, IX) to optimize both STING binding affinity and oral bioavailability. This involves adjusting molecular weight, lipophilicity, hydrogen bonding capacity, and other physicochemical parameters to achieve compounds that satisfy both efficacy and pharmacokinetic requirements simultaneously.
2Reliability
If compounds are designed to be potent STING activators, then therapeutic effectiveness is improved, but complexity of compound structure may increase
Solution Approach 1:
The patent employs segmentation by dividing the STING activator molecules into distinct functional domains represented by multiple substitutable groups (R1-R10, X1-X6, Z1-Z6) in formulae A, I, II, III, IV, V, VI, VII, VIII, and IX. This modular structure allows optimization of potency while maintaining manageable structural complexity through systematic variation of individual segments.
Solution Approach 2:
The patent achieves universality by creating a broad class of compounds with multiple substitutable positions that can accommodate various functional groups while maintaining core STING activation activity. This multi-functional framework allows a single molecular scaffold to serve multiple therapeutic purposes across different disease indications.
3Adaptability or versatility
If compounds are developed for multiple disease indications, then versatility is improved, but development time and resources increase
Solution Approach 1:
The patent achieves versatility through universal compound formulae (A, I, II, III, IV, V, VI, VII, VIII, IX) that can address multiple disease indications including viral infections, cancer, autoimmune diseases, and inflammatory conditions. The modular structure allows a single compound class to be adapted for different therapeutic applications without requiring complete redesign.
Solution Approach 2:
The patent applies preliminary action by establishing a validated compound framework with defined structural features and activity relationships before targeting specific diseases. This pre-established molecular platform enables rapid adaptation to different indications, reducing development time compared to de novo compound design for each disease.
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
These compounds effectively stimulate the innate immune response, upregulate STING activity, and increase interferon-beta levels, providing therapeutic benefits for inflammatory diseases, autoimmune diseases, infectious diseases, and cancer, and can be used as vaccine adjuvants.
Implementation Method 1
Activation of STING by CDNs, generated in response to cytosolic DNA, results in up-regulation of IRF3 and NFκB pathways leading to induction of interferon beta (INF-β) and other cytokines
Data Source
AI summary
Provided herein are compounds of the general formula (I):and pharmaceutically acceptable salts thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.