Myc-Max Inhibitor Design for Reduced Concentration
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Solution Overview
Problem
Current Myc-Max compounds have low potency, requiring concentrations of 50-100 μM to inhibit tumor cell growth effectively, limiting their clinical utility.
Innovation Solution
Development of novel chemical analogs with modified six- and five-member rings, such as 10058-F4 derivatives, which interfere with the association between c-Myc and Max, enhancing their ability to inhibit cell growth and proliferation at lower concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current Myc-Max compounds are used to inhibit tumor cell growth, then inhibition of c-Myc-Max association is achieved, but high concentrations (50-100 μM) are required which limits clinical utility
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structure parameters of the Myc-Max compounds. Specifically, different substituents (R1-R6) are introduced at various positions of the core structure, including electron-withdrawing groups like fluorine and chlorine atoms, to optimize the binding affinity and potency of the compounds against c-Myc-Max association, thereby reducing the required concentration for effective inhibition
Solution Approach 2:
The patent employs composite materials by creating complex substituted benzylidene rhodanine structures that combine multiple functional groups and aromatic rings. These composite molecular structures enhance the interaction with the c-Myc-Max interface, improving inhibition efficacy at lower concentrations compared to simpler analogs
2Reliability
If concentration of Myc-Max compounds is increased to improve inhibition efficacy, then tumor cell growth inhibition is enhanced, but off-target effects and toxicity may increase
Solution Approach 1:
The patent applies local quality by introducing specific substituents at particular positions (R1-R6) of the molecular structure to enhance local interactions with the c-Myc-Max binding interface. This localized optimization of binding affinity allows for selective inhibition at lower concentrations, reducing the need for high doses that would cause off-target effects
Solution Approach 2:
The patent replaces the mechanical approach of simply increasing compound concentration with a molecular design strategy that substitutes structural optimization. By carefully designing the chemical structure to maximize specific interactions with c-Myc-Max, the patent achieves high efficacy at low concentrations, avoiding the toxicity associated with high-dose administration
Data Source
AI summary
Compounds and compositions for interfering with the association of Myc and Max are described herein. These compounds and compositions are useful in methods inhibiting growth or proliferation of a cell. Methods of inhibiting growth or proliferation of a cell are provided, comprising contacting the cell with an amount of a compound that interferes with Myc and Max association effective to inhibit growth or proliferation of the cell.