Sestrin-GATOR2 Interaction Modulators for Selective mTORC1 Control
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Solution Overview
Problem
Current therapies fail to effectively modulate mTORC1 activity, which is dysregulated in various diseases including diabetes, epilepsy, neurodegeneration, immune response, and cancer, due to the lack of targeted modulation of the Sestrin-GATOR2 complex.
Innovation Solution
Development of compounds that act as Sestrin-GATOR2 modulators, specifically targeting the Sestrin-GATOR2 interaction to indirectly regulate mTORC1 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used to modulate mTORC1 activity, then treatment of mTORC1 dysregulation is attempted, but the modulation is not effective due to lack of targeted modulation of the Sestrin-GATOR2 complex
Solution Approach 1:
The patent introduces compounds that specifically target the Sestrin-GATOR2 complex as an intermediary to indirectly modulate mTORC1 activity. Instead of directly acting on mTORC1, the compounds bind to the Sestrin-GATOR2 interface, disrupting or stabilizing this interaction to achieve indirect control over mTORC1 signaling pathways.
Solution Approach 2:
The patent modifies the interaction parameters between Sestrin and GATOR2 by introducing small molecule compounds that alter the binding affinity, interaction strength, or complex stability. These parameter changes in the Sestrin-GATOR2 interaction translate to downstream effects on mTORC1 activity, enabling fine-tuned modulation.
2Adaptability or versatility
If broad-spectrum mTORC1 modulation is applied, then various diseases may be treated, but selectivity and precision of modulation is reduced
Solution Approach 1:
The patent employs compounds with specific molecular structures designed to target the unique structural features of the Sestrin-GATOR2 interface. By focusing on local structural characteristics of this specific protein-protein interaction site, the compounds achieve high selectivity for Sestrin-GATOR2 modulation while indirectly affecting mTORC1, thereby maintaining precision despite broad therapeutic applications.
Solution Approach 2:
By using Sestrin-GATOR2 as an intermediary target rather than directly modulating mTORC1, the patent achieves indirect and selective control over mTORC1 activity. This intermediary approach allows for precise modulation at the Sestrin-GATOR2 interface that translates to downstream effects on mTORC1, enabling selective treatment across multiple disease conditions.
Data Source
AI summary
The present invention provides compounds, compositions thereof, and methods of using the same.