3'3'-Cyclic Dinucleotide STING Modulation via Phosphonomethoxy Group
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for novel cyclic dinucleotides that activate the STING protein to effectively treat diseases such as viral infections, autoimmune diseases, and cancer, as existing compounds may not adequately modulate STING activity for therapeutic benefits.
Innovation Solution
Development of a compound of Formula (I), a 3′3′-cyclic dinucleotide with a phosphonomethoxy group that binds to and modulates the STING protein, activating it to induce the production of type I interferons, cytokines, and chemokines, thereby enhancing immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing cyclic dinucleotide compounds are used to activate STING protein, then immune response is stimulated, but therapeutic efficacy is insufficient for treating diseases such as viral infections, autoimmune diseases, and cancer
Solution Approach 1:
The patent modifies the chemical structure of cyclic dinucleotides by introducing a phosphonomethoxy group at the 3' position (Formula I compounds), changing the molecular parameters to achieve both potent STING activation and therapeutic efficacy. This structural parameter change resolves the contradiction by creating compounds that are more effective than existing cyclic dinucleotides while maintaining the ability to modulate STING protein.
2Reliability
If novel 3'3'-cyclic dinucleotides with phosphonomethoxy group are developed, then STING activation and immune response are enhanced, but compound complexity increases
Solution Approach 1:
The compound is divided into distinct functional segments: the cyclic dinucleotide core structure that binds STING, and the phosphonomethoxy group at the 3' position that enhances activation. This segmentation allows the molecule to perform multiple functions while maintaining a relatively simple overall structure that is feasible for synthesis and therapeutic use.
Data Source
AI summary
The present disclosure relates to 3′3′ cyclic phosphonate dinucleotides of general formula (I), their pharmaceutically acceptable salts, their pharmaceutical composition and combinations of the substances and other medicaments or pharmaceuticals. The disclosure also relates to compounds for the treatment or prevention of diseases or conditions modifiable by STING protein modulation, such as cancer or viral, allergic and inflammatory diseases.