PCNA Inhibitors Selective Targeting Cancer Cells
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Solution Overview
Problem
Current strategies for developing therapeutically tractable compounds targeting the cancer-associated isoform of proliferating cell nuclear antigen (caPCNA) have been limited in success.
Innovation Solution
A compound or its pharmaceutically acceptable salt, characterized by a specific formula, is provided, which has the potential to selectively target and inhibit PCNA activity, thereby treating diseases associated with PCNA activity, including cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide and small molecule-based inhibitors are used to target caPCNA, then therapeutic targeting of cancer cells is attempted, but the success in developing therapeutically tractable compounds has been limited
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structures (changing molecular weight, functional groups, stereochemistry, and substitution patterns) to optimize inhibitor efficacy and selectivity for caPCNA. This is evident in the extensive series of compounds with varying R groups, ring structures, and molecular weights that were screened to identify therapeutically tractable compounds.
2Object-affected harmful factors
If selective targeting of cancer cells is achieved, then side effects are reduced, but the complexity of achieving selectivity increases
Solution Approach 1:
The patent applies local quality by designing compounds with specific functional groups and molecular features that selectively interact with caPCNA structures unique to cancer cells. The inhibitors are engineered with particular stereochemistry, substitution patterns, and functional group arrangements that exploit local structural differences between caPCNA and normal PCNA, enabling selective cancer cell targeting.
Solution Approach 2:
The patent uses the caPCNA protein itself as an intermediary to achieve selective cancer cell targeting. By designing inhibitors that specifically bind to the cancer-associated isoform caPCNA, the therapy exploits the presence of this intermediary marker in cancer cells to deliver selective inhibition, thereby sparing normal cells that express only the wild-type PCNA.
Data Source
AI summary
Described herein, inter alia, are PCNA inhibitors and uses thereof.