3'3' Cyclic Dinucleotides With Isonucleotide Units for STING Activation
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Solution Overview
Problem
There is a need for novel cyclic dinucleotides that effectively activate the STING protein to stimulate interferon and cytokine production for the treatment of diseases such as inflammation, autoimmune diseases, cancer, and viral infections, as well as serve as vaccine adjuvants.
Innovation Solution
Development of 3'3' cyclic dinucleotides with isonucleotide units, where one or both nucleotide units are shifted from the 1' position to the 2' position, which bind to and activate the STING protein, stimulating interferon and cytokine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cyclic dinucleotides are used to activate STING protein, then immune response is stimulated, but novel compounds with improved efficacy and selectivity are needed
Solution Approach 1:
The patent applies parameter changes by modifying the nucleotide structure parameters - specifically creating isonucleotide units where the base is attached to the 2' position instead of the conventional 1' position of the sugar ring. This structural parameter change generates novel cyclic dinucleotides with improved STING activation efficacy while maintaining the essential cyclic dinucleotide framework.
Solution Approach 2:
The invention creates composite molecular structures by combining isonucleotide units with specific sugar-phosphate backbones to form hybrid cyclic dinucleotide structures. These composite structures integrate the modified isonucleotide component with the essential cyclic dinucleotide framework, producing compounds that exhibit enhanced STING activation compared to conventional nucleotides.
2Adaptability or versatility
If isonucleotide units with base at 2' position are used, then novel STING agonists are created, but synthesis complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the cyclic dinucleotide into modular isonucleotide units that can be independently synthesized and then assembled. Each isonucleotide unit consists of a sugar component with a 2'-position base attachment and a phosphate group, allowing for systematic construction of the cyclic structure through standardized linkage reactions.
Solution Approach 2:
The invention systematically varies parameters within the isonucleotide structure - including different sugar configurations, base types, and phosphate linkages - to generate a library of analogs with varying STING activation profiles. This parameter-based approach allows for rational optimization of both efficacy and synthesis feasibility.
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
The 3'3' cyclic dinucleotides with isonucleotide units effectively activate the STING protein, inducing interferon and cytokine responses, providing therapeutic benefits in treating inflammation, autoimmune diseases, cancer, and viral infections, and enhancing vaccine efficacy.
Implementation Method 1
The 3'3' cyclic dinucleotides with isonucleotide units effectively activate the STING protein, inducing interferon and cytokine responses
Data Source
AI summary
The present disclosure relates to 3'3' cyclic dinucleotides containing isonucleotidic units, their pharmaceutically acceptable salts, their pharmaceutical composition and combinations of said substances and other medicaments or pharmaceuticals. The disclosure also relates to the use of said compounds for the treatment or prevention of diseases or conditions modifiable by STING protein modulation, such as cancer or viral, allergic and inflammatory diseases. In addition, these substances can be used as adjuvants in vaccines. The compounds have formula (J):