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Small Molecule Activates Innate Immune Responses Controlled by the Human Protein STING
Oregon Health and Science University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• A small molecule termed M04 that behaves as a novel agonist of human STING. Also, the molecule exhibits a differential ability to activate STING based on the allelic variant examined.
• STING functions to activate innate immune (especially type I interferon) responses, which can impair viral replication, and initiate adaptive immune processes including antibody and T cell-mediated activity against microbial pathogens and tumor cells.
• Inventors have developed a novel small molecule agonist of STING, which may overcome some of the chemical liabilities of current STING inducers, as a potential anti-cancer therapy.
• Testing in human peripheral blood mononuclear cells (PBMCs) taken from patients with pancreatic cancer found that treatment with the STING agonist induced several cytokines illustrative of the compound’s ability to induce innate responses necessary for adaptive immunity. Testing in healthy human PBMCs also found the agonist was capable of facilitating maturation of antigen presenting cells (APC) and increased in the frequency of antigen-specific CD8+ T cells, indicating its adjuvant properties.
WO2021262878A1
Characterization of a Novel Compound That Stimulates STING-Mediated Innate Immune Activity in an Allele-Specific Manner. Front Immunol. (2020)
