Linked Myc-Max Inhibitors Disrupt Protein Interaction
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Solution Overview
Problem
Current methods for specifically inhibiting the c-Myc oncoprotein, particularly in cancer treatment, face challenges due to low potency and delivery issues with existing inhibitors, as well as the redundancy and cell type-specificity of transforming c-Myc target genes.
Innovation Solution
Development of small molecules that disrupt the interaction between c-Myc and its binding partner Max by linking moieties that bind to c-Myc, enhancing binding affinity through synergistic effects, and using flexible linkers to target different binding sites on the c-Myc protein.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule inhibitors are used to target c-Myc, then therapeutic benefit is achieved, but potency is insufficient
Solution Approach 1:
The patent combines multiple c-Myc binding moieties into a single bivalent molecule through a linker, creating a compound that can simultaneously bind to multiple sites on the c-Myc protein. This merging of binding functions increases overall binding affinity and potency compared to monovalent inhibitors, directly resolving the contradiction between achieving therapeutic benefit and maintaining sufficient potency.
2Strength
If multiple binding sites on c-Myc are targeted, then binding affinity increases, but molecule complexity increases
Solution Approach 1:
The patent segments the c-Myc protein into multiple binding sites and designs a bivalent inhibitor that targets these distinct segments simultaneously. By dividing the inhibition function across multiple binding moieties connected by a linker, the patent achieves high binding affinity through multivalent binding while maintaining a relatively simple molecular architecture that is manageable for drug development.
3Reliability
If existing inhibitors are used, then delivery is required, but delivery issues limit effectiveness
Solution Approach 1:
The patent changes the physical and chemical parameters of the inhibitor by creating a bivalent molecule with increased molecular weight, multiple binding domains, and potentially altered solubility characteristics. These parameter changes enable the inhibitor to achieve sufficient potency at lower concentrations and may improve pharmacokinetic properties, thereby reducing delivery challenges and enhancing overall effectiveness.
Data Source
AI summary
Provided herein are compounds and compositions for interfering with the association of Myc and Max. These compounds and compositions are useful in methods for inhibiting growth or proliferation of a cell. Methods of inhibiting growth or proliferation of a cell comprise 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.