Cyclic Di-Nucleotide STING Agonists for Interferon Production
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Solution Overview
Problem
There is a need for new agents that can induce potent type I interferon production, which is crucial for antiviral and anti-cancer therapies, as existing compounds have limitations in activating the STING pathway effectively.
Innovation Solution
Development of novel cyclic di-nucleotide compounds and their derivatives that act as STING agonists, inducing STING-dependent type I interferon production and immune responses, potentially used in combination with other therapeutic agents for treating cell proliferation disorders like cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds are used to activate the STING pathway, then some immune response is generated, but the type I interferon production is insufficient and not potent enough for effective antiviral and anti-cancer therapy
Solution Approach 1:
The patent modifies the chemical structure of cyclic di-nucleotide compounds by changing parameters such as the nucleotide composition (2′3′-cGAMP core structure), ring configuration, and substituent groups to optimize STING pathway activation. These structural parameter changes result in compounds that induce potent type I interferon production, directly resolving the insufficient efficacy of existing compounds while maintaining therapeutic versatility.
2Reliability
If the STING pathway is activated to induce type I interferon production, then antiviral and anti-tumor activities are enhanced, but the complexity of compound design and synthesis increases
Solution Approach 1:
The cyclic di-nucleotide compounds are designed with a segmented modular structure consisting of a core 2′3′-cGAMP structure and variable substituent groups. This segmentation allows systematic optimization of different regions: the core structure ensures STING pathway activation, while modular substituents can be tailored to enhance specific therapeutic activities. This reduces design complexity compared to completely novel structures while maintaining potent immune response induction.
Solution Approach 2:
The patent uses the cyclic di-nucleotide compounds as intermediary molecules that bridge the gap between synthetic chemistry and biological activity. These compounds serve as mediators that specifically interact with the STING protein to trigger the immune response pathway. By designing these intermediary compounds with optimized structures, the patent achieves reliable immune response induction without requiring overly complex molecular designs.
Data Source
AI summary
A class of polycyclic compounds of general formula (I), wherein Base1, Base2, Y, Za, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, R8a, and R9 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.