Small Molecule Modulators for Nucleic Acid Splicing
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Solution Overview
Problem
Current therapies for modulating RNA expression, such as oligonucleotide targeting and gene therapy, face challenges in effectively regulating alternative splicing patterns, which are often associated with diseases.
Innovation Solution
Development of small molecule compounds, specifically those of Formulas (I) and (II), that can modulate nucleic acid splicing by binding to or forming complexes with nucleic acids or proteins involved in the splicing process, thereby altering splicing patterns.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If oligonucleotide targeting or gene therapy is used to modulate RNA expression, then RNA expression can be targeted, but the ability to effectively regulate alternative splicing patterns is limited
Solution Approach 1:
The patent changes the chemical parameters from oligonucleotides to small molecule compounds with specific chemical structures (Formula I and Formula II), enabling effective regulation of alternative splicing patterns while maintaining RNA expression modulation capabilities
Solution Approach 2:
The invention uses composite chemical structures combining multiple functional groups (indazolylidene, pyrimidinone, pyridine rings with various substituents) to create small molecules that can effectively target and regulate splicing machinery, overcoming the limitations of single-modality approaches
2Adaptability or versatility
If small molecule compounds are developed to target splicing, then splicing modulation capability is improved, but the complexity of the chemical structure increases
Solution Approach 1:
The small molecule compounds are divided into distinct structural segments (indazolylidene core, pyrimidinone ring, pyridine ring with substituents R1-R6) that can be independently optimized, allowing complex splicing modulation capability while maintaining manageable structural complexity through modular design
Solution Approach 2:
The core structural framework (indazolylidene-pyrimidinone-pyridine) serves multiple functions: binding to splicing machinery, regulating alternative splicing patterns, and providing a platform for optimizing pharmacological properties through substituent variation, thereby achieving high adaptability without proportional increases in complexity
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 compounds effectively modulate splicing events, impacting the level of gene products produced, and have the potential to prevent and treat various diseases, including proliferative and non-proliferative conditions, by targeting aberrant splicing patterns.
Implementation Method 1
binding to or forming complexes with nucleic acids or proteins involved in the splicing process
Data Source
AI summary
The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.