Azurin Peptide Stabilizes P53 to Prevent Premalignant Lesions

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Solution Overview

Problem

Current chemopreventive therapies for cancer lack effective agents that can selectively target and inhibit the development of premalignant lesions without harming normal cells, as they often fail to differentiate between cancerous and non-cancerous cells.

Innovation Solution

The use of cupredoxin-derived peptides, such as azurin and its variants, which selectively enter cancer cells, stabilize p53, and prevent its ubiquitination, thereby inhibiting cancer cell growth and preventing the formation of premalignant lesions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemopreventive therapies are used, then cancer treatment is provided, but they harm normal cells along with cancer cells due to inability to differentiate

Engineering Contradiction:
Improveselectivity of cancer targetingVSAvoiddamage to normal cells
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by modifying the chemopreventive agent to exhibit different properties in different cellular environments. The agent is designed to be activated or become effective specifically within cancer cells through mechanisms such as selective uptake, intracellular processing, or pH-dependent activation, thereby exerting its chemopreventive effect locally at the cancer cell site while remaining inactive or less active in normal cells.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by altering the chemical, physical, or biological parameters of the chemopreventive agent to achieve selective cancer cell targeting. This may involve changing the agent's solubility, charge, size, or molecular structure to exploit differences between cancer and normal cells, such as enhanced permeability and retention effect in tumors or differential expression of transporters, thereby improving selectivity without harming normal cells.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If chemopreventive agents are designed to be highly selective for cancer cells, then normal cells are protected, but the complexity of the therapy increases

Engineering Contradiction:
Improveselectivity of cancer targetingVSAvoidcomplexity of chemopreventive therapy
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies self-service by designing chemopreventive agents that automatically achieve selective cancer cell targeting through their inherent properties without requiring complex external control systems. The agents may self-assemble, self-activate, or self-target cancer cells based on their molecular characteristics and the biological differences between cancer and normal cells, thereby achieving high selectivity while minimizing therapeutic complexity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent utilizes intermediaries by employing carrier molecules, targeting ligands, or delivery vehicles that mediate the selective delivery of chemopreventive agents to cancer cells. These intermediaries facilitate selective uptake or binding to cancer cells through specific interactions such as receptor-ligand binding or antibody-antigen recognition, thereby achieving high selectivity while the intermediary itself manages the complexity of the targeting mechanism.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS9598470B2Compositions and methods to prevent cancer by stabilizing P53 through non MDM2-mediated pathways
Publication Date: 2017.03.21 THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
  • US9598470B2 patent drawing
  • US9598470B2 patent drawing
  • US9598470B2 patent drawing

AI summary

The present invention relates to compositions and methods comprising chemopreventive agents that may be cupredoxin(s) or variants, derivatives and structural equivalents of cupredoxins, and at least one other chemopreventive agent. Specifically, these compositions may comprise azurin from Pseudomonas aeruginosa, and/or the 50-77 residue region of azurin (p28). The compositions of the invention may be used to prevent or inhibit the development of premalignant lesions in mammalian cells, tissues and animals, and thus prevent cancer.