Covalent USP7 Inhibitor Scaffolds for Potency and Selectivity
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Solution Overview
Problem
Current USP7 inhibitors exhibit modest potency and poor selectivity, solubility, and toxicity, limiting their effectiveness in targeting USP7 for therapeutic applications.
Innovation Solution
Development of small molecule USP7 inhibitors that covalently bind to USP7, featuring specific structural formulas with varying substituents and linkages, enhancing potency and selectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known USP7 inhibitors are used, then USP7 inhibition is achieved, but potency is modest and selectivity is poor
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of USP7 inhibitors through varying substituents (R1-R4, Ring B) and linkages (L1, L3) to optimize potency and selectivity while reducing toxicity and improving solubility
Solution Approach 2:
The patent employs local quality by introducing specific functional groups and substituents at particular positions in the inhibitor structure to enhance binding affinity for USP7 while maintaining selectivity against other DUBs
2Adaptability or versatility
If polypharmacological DUB inhibitors are used, then broad DUB family coverage is achieved, but potency toward primary target is weak
Solution Approach 1:
The patent uses local quality by designing inhibitors with specific structural features that target USP7's unique active site characteristics, achieving high potency and selectivity for USP7 while maintaining the ability to inhibit other DUBs
Solution Approach 2:
The patent applies universality by creating a inhibitor scaffold that can interact with multiple DUB family members while maintaining optimized potency for USP7 through specific substituent variations
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
The developed inhibitors demonstrate improved potency and selectivity against USP7, providing potential therapeutic benefits for treating diseases modulated by USP7, including cancer.
Implementation Method 1
small molecule USP7 inhibitors that covalently bind to USP7
Data Source
AI summary
Disclosed herein are inhibitors of deubiquitinating (DUB) enzyme USP7 (Ubiquitin Specific Protease 7). Also provided are methods of treating a disease or disorder modulated by USP7.