STING Antagonist Compounds for Autoinflammatory Disorder Treatment
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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), (II), and (III), or their pharmaceutically acceptable salts, which directly bind or modify STING to inhibit its activity, thereby blocking agonist-mediated responses and reducing excessive STING signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If STING signaling is activated to fight cancer and infections, then immune response is enhanced, but excessive STING activation causes harmful inflammation and autoinflammatory disorders
Solution Approach 1:
The patent applies parameter changes by developing small molecule compounds that selectively modulate STING signaling at different intensity levels. The compounds change the activation parameter of STING from excessive (pathological) to controlled (therapeutic), enabling the same pathway to treat both cancer (needs activation) and autoinflammatory disorders (needs suppression) depending on the specific compound and dosing regime.
Solution Approach 2:
The patent uses small molecule compounds as intermediary substances that mediate between the STING pathway and the desired therapeutic outcome. These intermediaries (compounds of Formula I, II, or III) can either enhance or suppress STING signaling depending on the disease context, acting as controllable mediators to achieve the desired immune response level without direct manipulation of the STING pathway itself.
2Adaptability or versatility
If small molecule compounds are developed to inhibit STING, then treatment options for autoinflammatory disorders are improved, but lack of existing pharmacological interventions currently limits effective management
Solution Approach 1:
The patent applies universality by creating small molecule compounds with multiple therapeutic applications. The same compound class (Formula I, II, or III) can treat different conditions including cancer, autoinflammatory disorders, and viral infections by modulating STING signaling appropriately. This multi-functional approach allows one set of compounds to address multiple disease states that currently lack effective treatments.
3Measurement precision
If chemical entities are designed to bind STING, then selective inhibition is achieved, but complexity of compound structure increases
Solution Approach 1:
The patent applies local quality by focusing the inhibitory action of the compounds on specific local regions of the STING protein. The compounds of Formula I, II, or III are designed to bind to particular domains or pockets of STING, achieving selective inhibition through localized interaction rather than requiring complex overall molecular structures. This allows precise targeting with relatively simple molecular frameworks.
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 type I interferon production and alleviating disease symptoms.
Implementation Method 1
chemical entities (e.g., a compound or a pharmaceutically acceptable salt) 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.