Bromodomain Inhibitor Design for Selective Protein Binding
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Solution Overview
Problem
Current treatments lack effective methods to inhibit the aberrant activity of bromodomain-containing proteins, which are associated with various diseases including cancers, inflammatory diseases, and viral infections, as existing therapies fail to specifically target these proteins without causing unintended effects.
Innovation Solution
Development of compounds that bind to bromodomain-containing proteins, inhibiting their activity and function, thereby modulating transcriptional processes and reducing the expression of genes regulated by these proteins, which are formulated into pharmaceutical compositions for therapeutic and prophylactic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to treat diseases associated with bromodomain-containing proteins, then treatment is provided, but the therapies fail to specifically target these proteins causing unintended effects
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular structures that selectively interact with bromodomain-containing proteins. The compounds feature specific functional groups and structural motifs that confer selective binding affinity to the bromodomain region, enabling targeted inhibition without affecting other proteins, thus resolving the contradiction between treatment effectiveness and lack of specificity.
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters of the compound structures, such as substituent groups, stereochemistry, and molecular size, to optimize binding specificity to bromodomain-containing proteins. These parameter modifications enable the compounds to achieve high specificity and selectivity, thereby eliminating unintended effects while maintaining therapeutic efficacy.
2Reliability
If compounds are developed to bind bromodomain-containing proteins, then aberrant activity is inhibited, but the complexity of compound structure increases
Solution Approach 1:
The patent applies segmentation by dividing the molecular structure into distinct functional segments: a core scaffold portion that provides structural framework and a substituent portion that confers specific binding affinity to bromodomain-containing proteins. This modular segmentation allows for systematic optimization of inhibitory activity while managing structural complexity through standardized building blocks.
Solution Approach 2:
The patent employs universality by designing a core compound scaffold that can serve multiple functions: binding to bromodomain-containing proteins, inhibiting aberrant activity, and providing a framework for further structural optimization. This universal scaffold approach reduces the need for entirely new molecular designs, thereby managing complexity while achieving reliable inhibition across different disease states.
Data Source
AI summary
The present invention provides compounds of any one of Formulae (I), (II-C) (e.g., Formula (II)), and (III), and pharmaceutically compositions thereof. Compounds of any one of Formulae (I), (II-C), and (III) are believed to be binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.