13-Membered Ribosome Targeting Compounds for Nonsense Mutation Readthrough
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Solution Overview
Problem
Current treatments for genetic diseases caused by nonsense and frameshift mutations resulting in premature termination codons are inadequate, leading to an unmet need for effective compounds that can induce readthrough of these mutations.
Innovation Solution
Development of specific compounds, represented by Formula I, which are administered to promote readthrough of premature termination codons, comprising a therapeutically effective amount of a compound with defined structural parameters, including various substituents and functional groups, to treat genetic diseases associated with nonsense and frameshift mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for genetic diseases caused by nonsense mutations, then current standard care is maintained, but effective treatment is not achieved
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of compounds to optimize their ability to induce readthrough of premature termination codons. The formula I compounds incorporate specific substituents (R1-R11 groups) that can be adjusted to enhance efficacy against different nonsense mutations while maintaining safety profiles, thereby improving treatment effectiveness across various genetic diseases
Solution Approach 2:
The patent achieves universality by developing a broad class of compounds (formula I) that can treat multiple different genetic diseases caused by nonsense mutations. The general structure with variable substituents allows a single compound class to address diverse conditions such as cystic fibrosis, Duchenne muscular dystrophy, and other genetic disorders, making the treatment approach universally applicable
2Reliability
If readthrough compounds are developed to treat nonsense mutations, then treatment effectiveness is improved, but compound complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the compound structure into distinct functional modules: a core scaffold (formula I) and variable substituent groups (R1-R11). This modular approach allows optimization of readthrough induction capability through specific substituent selection while maintaining manageable structural complexity through systematic organization of the molecular components
Solution Approach 2:
The patent implements local quality by introducing specific functional groups and substituents at particular positions in the molecule (R1-R11 locations) to enhance readthrough activity. Each substituent position can be optimized independently to achieve the desired biological activity while controlling overall molecular complexity through targeted modification rather than complete structural redesign
Data Source
AI summary
Provided are 13-membered ribosome targeting compounds that can be used to treat genetic diseases, including genetic diseases that are associated with a premature termination codon mutation or other nonsense mutation. The compounds can induce and/or promote readthrough of the premature termination codon mutation. Also provided are pharmaceutical compositions containing the compounds, methods of using the compounds and processes for making the compounds.