STING Agonists Overcoming Species Selectivity
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Solution Overview
Problem
Current small molecule STING agonists face limitations due to their large molecular weight, polarity, and species selectivity, which restricts their application as human therapeutics for modulating STING protein activity in treating diseases.
Innovation Solution
Development of novel compounds of Formula I, which are potent and selective modulators of the STING protein, overcoming the limitations of existing CDN-derived ligands by providing a pharmaceutical composition for therapeutic use in humans.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CDN derived ligands are used as STING agonists, then pre-clinical promise is achieved, but large molecular weight and polarity limit application to intratumoral injection
Solution Approach 1:
The patent applies parameter changes by modifying the molecular weight and polarity parameters of STING agonists. The invention describes small molecule compounds with optimized physicochemical properties that maintain STING activation capability while achieving systemic administration feasibility, directly addressing the molecular weight and polarity limitations of CDN derived ligands
2Reliability
If CDN derived ligands are used as STING agonists, then pre-clinical promise is achieved, but polarity limits application to intratumoral injection
Solution Approach 1:
The patent modifies the polarity parameter of STING agonists by designing small molecule compounds with optimized lipophilicity and membrane permeability properties. This enables transition from intratumoral injection to systemic administration routes such as oral or intravenous delivery
3Reliability
If small molecule STING agonists DMXAA and CMA are administered systemically, then therapeutic efficacy is achieved, but species selectivity prohibits use as human therapeutics
Solution Approach 1:
The patent applies universality by designing small molecule STING agonists with broad species applicability. The compounds are engineered to activate human STING protein effectively while maintaining the ability to function across different species, eliminating the species selectivity barrier that prevents clinical translation
Data Source
AI summary
Compounds of Formula I or pharmaceutically acceptable salts or esters thereof capable of binding to and modulating the activity of a stimulator of interferon genes (STING) protein are provided. Methods involving compounds of Formula I as effective modulators of STING are also provided.