Small Molecules Modulating FOXO3 NRF2 mTOR for Stress Resistance
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Solution Overview
Problem
Current compounds have not been shown to effectively extend human lifespan or healthy lifespan, and there are limited small molecules known to extend lifespan in experimental animals, with no effective solutions for increasing resistance to environmental stress or treating age-associated diseases.
Innovation Solution
Administration of stress resistance increasing compounds or their pharmaceutically acceptable salts to subjects to increase cellular stress resistance, lifespan, and treat age-associated diseases, while inhibiting cancer cell proliferation and survival, and modulating activities of FOXO3, NRF2, and mTOR proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If compounds are administered to increase cellular stress resistance and extend lifespan, then healthspan and longevity are improved, but no compound has been proven to effectively extend human lifespan yet
Solution Approach 1:
The patent uses small molecule compounds as intermediaries to modulate cellular stress response pathways (FOXO3, NRF2, mTOR) as a mediator between external intervention and lifespan extension. These compounds serve as chemical mediators that activate protective cellular mechanisms without directly extending lifespan, bridging the gap between known stress resistance pathways and longevity outcomes.
Solution Approach 2:
The invention changes the parameter of cellular stress resistance by administering compounds that modulate specific molecular pathways (FOXO3 activity, NRF2 activity, mTOR activity). By adjusting these biochemical parameters through compound administration, the patent aims to achieve lifespan extension while monitoring effectiveness through measurable cellular and molecular changes.
2Duration of action of stationary object
If small molecules are used to extend lifespan in experimental animals, then lifespan is extended, but the number of effective small molecules is limited
Solution Approach 1:
The patent identifies small molecules that can universally target multiple conserved longevity pathways (FOXO3, NRF2, mTOR) across different species. These compounds exhibit multi-functionality by simultaneously modulating stress resistance, autophagy, and metabolic pathways, making them broadly applicable for lifespan extension in various experimental models and potentially in humans.
Solution Approach 2:
The invention segments the complex lifespan extension problem into distinct molecular pathways (FOXO3-mediated stress resistance, NRF2-mediated antioxidant response, mTOR-mediated autophagy). By developing compounds that specifically target each pathway segment, the patent creates a library of specialized small molecules that can be combined or selected based on the specific biological context and desired outcome.
3Reliability
If compounds modulate FOXO3, NRF2, and mTOR activities to increase stress resistance, then cellular protection is improved, but the complexity of pathway modulation increases
Solution Approach 1:
The patent uses small molecule compounds as chemical intermediaries to simplify the complexity of modulating multiple cellular pathways. Each compound acts as a specific mediator that selectively targets one or more pathways (FOXO3, NRF2, or mTOR), converting the complex task of simultaneous pathway modulation into manageable single-target or dual-target interventions with predictable outcomes.
Data Source
AI summary
Disclosed herein, inter alia, are compounds and methods useful for increasing stress resistance.