Article ; Online: Discovery of IACS-8803 and IACS-8779, potent agonists of stimulator of interferon genes (STING) with robust systemic antitumor efficacy.
Bioorganic & medicinal chemistry letters
2019 Volume 29, Issue 20, Page(s) 126640
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 ...
| 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. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Antineoplastic Agents/chemistry ; Cell Line ; Cytosol/metabolism ; Heterocyclic Compounds/chemistry ; Heterocyclic Compounds/pharmacology ; Humans ; Immunity, Innate ; Immunotherapy/methods ; Interferon-beta/metabolism ; Melanoma/immunology ; Melanoma, Experimental/immunology ; Membrane Proteins/immunology ; Mice ; Nucleotides, Cyclic/antagonists & inhibitors ; Phosphates/metabolism ; Signal Transduction ; Tumor Microenvironment | |||||
| Chemical Substances | Antigens, Neoplasm ; Antineoplastic Agents ; Heterocyclic Compounds ; Membrane Proteins ; Nucleotides, Cyclic ; Phosphates ; Interferon-beta (77238-31-4) ; phosphorodithioic acid (8056RR93HU) | |||||
| Language | English | |||||
| Publishing date | 2019-08-24 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 1063195-1 | |||||
| ISSN | 1464-3405 ; 0960-894X | |||||
| ISSN (online) | 1464-3405 | |||||
| ISSN | 0960-894X | |||||
| DOI | 10.1016/j.bmcl.2019.126640 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 3203: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.