This technology features triazine derivatives designed to mimic the structure of the Mycobacterium tuberculosis antigen Rv3364c that binds to the host protein SNX9, as well as pharmaceutical and food compositions for preventing or treating sepsis using these derivatives as active ingredients. These compounds bind to SNX9 within macrophages to dampen excessive inflammatory signaling while simultaneously providing antimicrobial activity.
Sepsis is a condition where uncontrolled immune responses to infection lead to organ failure, with a mortality rate approaching 25%. Despite our understanding of its pathogenesis, targeted therapies remain scarce. While peptide-based therapies with high target specificity have been studied as alternatives, they face limitations in clinical development due to low in vivo stability and difficulties in targeted delivery.
Instead of peptides, this technology utilizes small molecules with a triazine backbone identified through virtual screening. By disrupting the binding of SNX9 and p47phox in early endosomes, it inhibits reactive oxygen species (ROS) production and NADPH oxidase activation, while reducing the secretion of inflammatory cytokines such as TNF-α and IL-6. It has demonstrated significantly higher therapeutic efficacy for sepsis compared to the original Rv3364c-derived peptide and also possesses antibacterial effects. Applicable to sepsis and septic shock treatments, therapies for bacterial infections like tuberculosis, and immune-modulating health supplements, this technology enables the development of a new drug pipeline that simultaneously targets excessive inflammation and pathogen clearance with a single small-molecule drug.
This invention was developed with support from the Ministry of Education for the analysis of host immune modulation mechanisms based on Toxoplasma gondii antigens and their therapeutic applications.
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