Abstract
Activation of the stimulator of interferon genes (STING) pathway by both exogenous and endogenous cytosolic DNA results in the production of interferon beta (IFN-β) and is required for the generation of cytotoxic T-cell priming against tumor antigens. In the clinical setting, pharmacological stimulation of the STING pathway has the potential to synergize with immunotherapy antibodies by boosting anti-tumor immune responses. We report the discovery of two highly potent cyclic dinucleotide STING agonists, IACS-8803 and IACS-8779, which show robust activation of the STING pathway in vitro and a superior systemic anti-tumor response in the B16 murine model of melanoma when compared to one of the clinical benchmark compounds.
Original language | English (US) |
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Article number | 126640 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 29 |
Issue number | 20 |
DOIs | |
State | Published - Oct 15 2019 |
Keywords
- Cyclic dinucleotide
- Immune response
- Phosphorothioate esters
- STING agonists
- T-cell priming
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry