IGF2BP1-RNA Binding Inhibitors for Kras Mutant Lung Cancer
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Solution Overview
Problem
Current therapies for lung cancers driven by Kras-activating mutations are ineffective, and there is a need for new treatments targeting IGF2BP1, which is upregulated in various cancers and synergizes with Kras to enhance oncogenic activity.
Innovation Solution
Development of compounds that inhibit IGF2BP1 binding to RNA, specifically represented by certain chemical formulas, which can be used in pharmaceutical compositions to treat cancers by reducing IGF2BP1 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule compounds targeting Kras downstream mediators are used, then some therapeutic intervention is provided, but clinical efficacy remains minimal in Kras mutant lung adenocarcinomas
Solution Approach 1:
The patent extracts and targets a specific RNA binding protein (IGF2BP1) that directly interacts with Kras mRNA, removing this critical regulatory element from the oncogenic pathway. By developing small molecule compounds that specifically inhibit IGF2BP1-RNA binding, the invention isolates and disrupts this particular interaction point in the Kras signaling pathway, achieving therapeutic effect where broader downstream mediator targeting failed.
Solution Approach 2:
The patent introduces small molecule compounds as intermediary substances that mediate between the therapeutic goal and the molecular target. These compounds serve as chemical mediators that bind to IGF2BP1 and prevent its interaction with RNA, thereby translating the therapeutic intent of inhibiting oncogenic signaling into concrete molecular disruption without directly targeting Kras itself or its immediate downstream effectors.
2Object-affected harmful factors
If IGF2BP1 expression is elevated in cancers, then oncogenic activity is enhanced through synergy with Kras, but this creates a specific therapeutic target for intervention
Solution Approach 1:
The patent applies local quality by developing compounds with specific molecular characteristics tailored to inhibit IGF2BP1-RNA binding. The small molecule compounds are designed with particular structural features (represented by the chemical formulas with specific substituents R1-R11) that enable selective interaction with IGF2BP1, creating a localized therapeutic effect at the molecular binding interface rather than broad-spectrum inhibition.
Solution Approach 2:
The patent utilizes parameter changes by modifying the binding parameters between IGF2BP1 and RNA through small molecule intervention. The compounds alter the thermodynamic and kinetic parameters of the protein-RNA interaction, changing the binding affinity and stability of the IGF2BP1-RNA complex, thereby converting the harmful high-affinity binding into a disrupted, low-affinity interaction that reduces oncogenic activity.
Data Source
AI summary
The present invention is directed to compounds and compositions comprising thereof. Further, methods of use such as for the treatment and prevention of a disorder associated with binding of IGF2BP1 to an RNA in a subject in need thereof are also provided.