Discovery of IACS-8803 and IACS-8779, potent agonists of stimulator of interferon genes (STING) with robust systemic antitumor efficacy.
Bioorg Med Chem Lett
; 29(20): 126640, 2019 10 15.
Article
in En
| MEDLINE
| ID: mdl-31500996
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-ß) 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Melanoma, Experimental
/
Interferon-beta
/
Heterocyclic Compounds
/
Melanoma
/
Antineoplastic Agents
/
Nucleotides, Cyclic
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
United States