Development of a light-activated STING agonist
Literature Information
Publication Date
2023-11-22
DOI
10.1039/D3OB01578E
Impact Factor
3.876
Authors
Steven E. Caldwell, Chasity P. Janosko
View Original
Abstract
The STING pathway is critical to innate immunity and is being investigated as a potential therapeutic target. Existing agents targeting STING suffer from several undesirable effects, particularly the possibility of systematic activation, which increases the risk of autoimmune disorders. In this proof-of-concept study, we report the development of a light-activated STING agonist, based on the potent compound SR-717. We first screened the activity of the non-caged agonist toward 5 human STING variants to identify the most viable target. A photocaged agonist was designed and synthesized in order to block an essential interaction between the carboxy acid group of the ligand with the R238 residue of the STING protein. We then investigated the selective activation of STING with the photocaged agonist, demonstrating an irradiation-dependent response. The development and characterization of this selective agonist expands the growing toolbox of conditionally controlled STING agonists to avoid systematic immune activation.
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Source Journal
Organic & Biomolecular Chemistry
CiteScore:
3.4
Self-citation Rate:
10.3%
Articles per Year:
1041
Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.
Recommended Compounds
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4-[(2-Fluoro-4-methylphenyl)amino]-6-[4-(2-hydroxyethyl)-1-piperazinyl]-7-methoxy-3-cinnolinecarboxamide
CAS Number:
1041852-85-0
Molecular Formula:
C23H27FN6O3
![2-Methyl-2-propanyl 4-[3-(aminomethyl)phenyl]-1-piperazinecarboxylate structure](https://static.chemtradehub.com/structs/889/889948-55-4-5c12.webp "2-Methyl-2-propanyl 4-[3-(aminomethyl)phenyl]-1-piperazinecarboxylate structure")
2-Methyl-2-propanyl 4-[3-(aminomethyl)phenyl]-1-piperazinecarboxylate
CAS Number:
889948-55-4
Molecular Formula:
C16H25N3O2
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