Boronic Acid Proteasome Inhibitors for Selective Cancer Targeting
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Solution Overview
Problem
There is a need for new and improved proteasome inhibitors to effectively target cancer cells while minimizing side effects on normal tissues, as existing proteasome inhibitors may have broad effects on cellular processes.
Innovation Solution
Development of specific boronic acid and ester compounds that inhibit peptidase activities of the proteasome, including constitutive and immunoproteasome, with a general formula (I) that can be used in pharmaceutical compositions for treating cell proliferative diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing proteasome inhibitors are used, then cancer cells are targeted, but side effects on normal tissues occur
Solution Approach 1:
The patent applies local quality by creating proteasome inhibitors with specific molecular structures (formula I) that have tailored pharmacological properties. The compounds are designed with specific substituent patterns and stereochemical configurations that enable selective binding to the proteasome enzyme, thereby achieving effective cancer cell targeting while minimizing off-target effects on normal tissues through precise molecular design
2Reliability
If proteasome inhibitors are developed to inhibit peptidase activities, then proteasome activity is reduced, but cellular processes are affected
Solution Approach 1:
The patent segments the proteasome inhibition function into specific peptidase activities (trypsin-like, chymotrypsin-like, and caspase-like) that can be selectively inhibited. By designing compounds that target specific catalytic sites within the proteasome, the invention achieves effective proteasome inhibition while potentially spares other cellular processes that do not rely on these specific peptidase activities
Solution Approach 2:
The patent employs parameter changes by systematically varying molecular parameters such as substituent types, stereochemical configurations, and structural conformations in the proteasome inhibitor compounds. This allows optimization of the compounds to achieve high-affinity binding to the proteasome while modifying pharmacological properties to reduce unwanted effects on broader cellular processes
Data Source
AI summary
The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.