STING Partial Agonists Modulating Immune Response and Toxicity
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Solution Overview
Problem
Current treatments for conditions associated with impaired STING signaling, such as cancer, lack effective agents that can modulate STING activity to induce an immune response without causing significant toxicity.
Innovation Solution
Development of chemical entities, including compounds that act as partial agonists of STING, which bind to STING to increase its activity while preventing full agonist activation, thereby inducing STING-dependent type I interferon production and an immune response with reduced toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If full agonists of STING are used to induce type I interferon production and immune response, then therapeutic efficacy is improved, but toxicity and adverse effects increase
Solution Approach 1:
The patent applies partial agonism by designing compounds that activate STING to a controlled extent rather than fully. The partial agonists provide sufficient immune stimulation to treat cancer and viral infections while avoiding the excessive activation that leads to toxicity and adverse effects associated with full agonists
Solution Approach 2:
The patent changes the activation parameter of STING from full activation to partial activation. By modifying the agonist compounds to be partial agonists, the degree of STING activation is adjusted to an optimal level that maintains therapeutic efficacy while reducing toxicity
2Reliability
If STING activity is increased to treat conditions with impaired STING signaling, then immune response is enhanced, but risk of adverse effects increases
Solution Approach 1:
The patent uses partial agonists to achieve partial activation of STING, which is sufficient to enhance immune response in conditions with impaired STING signaling while avoiding the excessive activation that causes adverse effects
3Productivity
If current treatments are used for cancer and other conditions, then treatment is provided, but effectiveness is insufficient due to lack of STING modulating agents
Solution Approach 1:
The patent introduces partial agonist compounds as intermediary substances that mediate between the STING pathway and the immune system. These compounds selectively modulate STING activity to produce desired immune responses without the limitations of current treatments
Solution Approach 2:
The patent changes the therapeutic parameter by introducing agents that specifically modulate STING activity, transforming the treatment approach from non-specific to targeted modulation of the STING pathway, thereby improving both effectiveness and therapeutic benefit
Data Source
AI summary
This disclosure features chemical entities (e.g., a compound that modulates (e.g., agonizes) Stimulator of Interferon Genes (STING), or a pharmaceutically acceptable salt, and/or hydrate, and/or coccrystal, and/or drug combination of the compound) that are useful, e.g., for treating a condition, disease or disorder in which a decrease or increase in STING activity (e.g., a decrease, e.g., a condition, disease or disorder associated with repressed or impaired 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 as well as other methods of using and making the same.