Novel compounds for reducing mitochondrial reactive oxygen species and their uses

Mitochondria-targeted Rubicon-p22phox inhibitor-based therapeutic for inflammatory bowel disease

This technology features mito-TIPTP, a novel compound designed to target mitochondria, along with pharmaceutical compositions for preventing and treating inflammatory and necrotic diseases, and food compositions for improving mitochondrial function. The compound inhibits the binding of Rubicon and p22phox on the outer mitochondrial membrane, thereby reducing mitochondrial reactive oxygen species (ROS) production.

Excessive reactive oxygen species (ROS) in mitochondria damage proteins and DNA, contributing to chronic conditions such as sepsis, inflammatory bowel disease, and aging-related disorders; elevated levels are particularly observed in patients with inflammatory bowel disease. However, existing anti-inflammatories, immunosuppressants, and biologics struggle to provide fundamental cures, with many patients failing to respond or losing efficacy over time. Furthermore, previous candidates targeting only cytosolic ROS were limited by their inability to directly regulate mitochondrial ROS.

By adding a mitochondria-targeting function to a peptide-mimetic compound that blocks the Rubicon-p22phox interaction, this technology effectively suppresses mitochondrial ROS even at low concentrations, restores mitochondrial metabolic function, and reduces reliance on cytosolic glycolysis. Potential indications include ulcerative colitis, Crohn's disease, sepsis, rheumatoid arthritis, and chronic obstructive pulmonary disease. This enables the development of products with a novel mechanism of action—mitochondria-targeted therapy—aimed at chronic inflammation patients who do not respond to existing treatments, applicable to IBD drugs, sepsis and acute lung injury therapies, and health supplements for fatigue recovery.

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Key Features:

• An active ingredient comprising a novel mitochondria-targeted compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof
• A pharmaceutical composition for preventing or treating inflammatory diseases by inhibiting the interaction between Rubicon and p22phox in mitochondria to suppress mitochondrial ROS production
• A pharmaceutical composition targeting one or more of inflammatory bowel disease, sepsis, rheumatoid arthritis, and chronic obstructive pulmonary disease
• A food composition that improves mitochondrial function by reducing mitochondrial ROS and decreasing cytosolic glycolysis

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This invention was developed with support from the Ministry of Science and ICT's Laboratory for Immune Control of NLRP3 Inflammatory Diseases based on Nano-AI Convergence Technology.

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