MYST KAT Inhibitor Compounds With Improved Selectivity
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Solution Overview
Problem
There is a need for new inhibitors of Lysine Acetyl Transferases (KATs) of the MYST family, particularly in the context of diseases such as cancer, as existing inhibitors are limited in efficacy and specificity.
Innovation Solution
Development of compounds that inhibit the activity of KATs such as TIP60, KAT6B, MOZ, HBO1, and MOF, which are formulated as pharmaceutical agents for use in treating cancer, potentially in combination with radiotherapy and/or chemotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing inhibitors are used to target MYST family KATs, then some inhibitory activity is achieved, but efficacy and specificity are limited
Solution Approach 1:
The patent applies local quality by designing inhibitors with specific structural features (aromatic rings, heteroatoms, substituents at defined positions) that create localized interaction zones within the molecule. These localized structural characteristics enable selective binding to specific MYST family members or bromodomain proteins, thereby improving specificity while maintaining inhibitory efficacy
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters such as substituent types (halogens, alkyl groups, heteroaryl groups), ring positions, and stereochemistry to optimize the balance between efficacy and specificity. By adjusting these molecular parameters, the inhibitors achieve enhanced selectivity for target proteins while maintaining potent inhibitory activity
2Measurement precision
If new compounds are developed to improve specificity, then selectivity increases, but development complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the inhibitor molecule into distinct functional modules: a core aromatic or heteroaryl structure, substituent groups at specific positions (R1-R6), and optional stereochemical elements. This modular segmentation allows for systematic optimization of specificity through combinatorial variation of individual modules without requiring complete redesign of the entire molecule
Solution Approach 2:
The patent employs universality by designing a core molecular scaffold that can accommodate multiple substituent variations while maintaining the fundamental binding interaction with MYST family KATs or bromodomain proteins. This universal core structure enables a series of derivatives to be developed from a single platform, reducing overall development complexity while achieving diverse specificity profiles
Data Source
AI summary
A compound of formula (1), or a pharmaceutical salt thereof: