MYST Family Histone Acetyltransferase Inhibitors for Cancer
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Solution Overview
Problem
Current therapies lack effective targets for modulating MYST family histone acetyltransferases (KATs) activity, particularly in cancer cells, where aberrant activity of KAT-5, KAT-6A, KAT-7, and KAT-8 contributes to disease progression.
Innovation Solution
Development of specific inhibitors targeting MYST family KATs, such as compounds with general formula I and I′, which are designed to inhibit KAT-5, KAT-6A, KAT-7, and KAT-8 activity, offering therapeutic potential for various cancers by disrupting their aberrant activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used, then treatment of cancers is provided, but effective targets for modulating MYST family KATs activity are lacking
Solution Approach 1:
The patent introduces MYST family KAT inhibitors as intermediary compounds that mediate between the therapeutic goal and the biological target. These inhibitors (compounds of formula I and I′) serve as chemical mediators that specifically bind to and modulate the activity of MYST family KATs, filling the gap in available therapeutic targets while maintaining reliable cancer treatment effectiveness
2Object-affected harmful factors
If MYST family KAT activity is inhibited, then cancer cell survival and proliferation are reduced, but specificity of inhibition among KAT family members must be maintained
Solution Approach 1:
The patent applies local quality by designing inhibitors with specific structural features (formula I and I′ with defined substituents R1, R2, R3, Ra, Ring A, and Z) that confer selective binding affinity for MYST family KATs. The molecular structure is locally optimized at specific regions to recognize and bind preferentially to MYST family enzymes rather than other KAT family members, achieving both cancer cell inhibition and enzymatic specificity
Solution Approach 2:
The patent utilizes parameter changes by systematically varying chemical parameters (substituent types, positions, and configurations in the molecular formula) to optimize the balance between inhibitory potency against cancer cells and specificity for MYST family KATs. Different substituent combinations allow fine-tuning of the inhibitor's biochemical parameters to achieve the desired selectivity profile
Data Source
AI summary
The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.