STING Antagonist Compounds for Autoinflammatory Pathology
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Solution Overview
Problem
Current treatments for conditions associated with excessive STING activation, such as cancer and autoinflammatory disorders, lack effective pharmacological interventions to inhibit STING signaling, leading to inadequate management of these diseases.
Innovation Solution
Development of chemical entities, including compounds of Formula (I) and their pharmaceutically acceptable salts, hydrates, cocrystals, or prodrugs, that directly bind or modify STING to inhibit its activity, thereby blocking agonist-mediated responses and reducing excessive signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If STING activation is increased to enhance immune response against intracellular pathogens, then antiviral protection is improved, but excessive STING activation causes autoinflammatory conditions and pathology
Solution Approach 1:
The patent applies parameter changes by developing small molecule compounds that modulate STING signaling at specific molecular levels. These compounds alter the activation threshold and duration of STING pathway, converting excessive pathological activation into controlled therapeutic inhibition, thereby treating autoinflammatory conditions while preserving necessary immune function
Solution Approach 2:
The patent introduces small molecule compounds as intermediary substances that selectively bind to STING protein and its interacting partners (such as TBK1 and IRF3). These intermediaries block the pathological signal transduction cascade without completely abolishing STING function, thereby resolving the contradiction between maintaining antiviral protection and preventing autoinflammation
2Reliability
If small molecule compounds are developed to inhibit STING signaling, then treatment efficacy for autoinflammatory disorders is improved, but drug development complexity and validation requirements increase
Solution Approach 1:
The patent segments the complex drug development process into modular components: (1) identification of STING-binding chemical entities, (2) validation of STING inhibition mechanism, (3) assessment of therapeutic efficacy in disease models, and (4) evaluation of safety profiles. This segmentation allows systematic progression through development stages while managing complexity
Solution Approach 2:
The patent incorporates feedback mechanisms through comprehensive preclinical testing including cellular assays, animal models of autoinflammatory diseases, and pharmacokinetic/pharmacodynamic studies. This feedback loop enables iterative optimization of compound structures and dosing regimens before clinical trials, reducing overall development complexity by identifying failures early
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 chemical entities effectively antagonize STING activity, providing a therapeutic approach to treat conditions like cancer and autoinflammatory disorders by reducing excessive STING signaling and its associated pathology.
Implementation Method 1
chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING)... compounds that, at the protein level, directly bind or modify STING
Data Source
AI summary
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.