Discovery of isonucleotidic CDNs as potent STING agonists with immunomodulatory potential

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00559980" target="_blank" >RIV/61388963:_____/22:00559980 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/22:10447061
Result on the web
<a href="https://doi.org/10.1016/j.str.2022.05.012" target="_blank" >https://doi.org/10.1016/j.str.2022.05.012</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.str.2022.05.012" target="_blank" >10.1016/j.str.2022.05.012</a>

Result language
angličtina
Original language name
Discovery of isonucleotidic CDNs as potent STING agonists with immunomodulatory potential
Original language description
Stimulator of interferon genes (STING) is an adaptor protein of the cGAS-STING signaling pathway involved in the sensing of cytosolic DNA. It functions as a receptor for cyclic dinucleotides (CDNs) and, upon their binding, mediates cytokine expression and host immunity. Besides naturally occurring CDNs, various synthetic CDNs, such as ADU-S100, have been reported to effectively activate STING and are being evaluated in clinical trials for the treatment of cancer. Here, we describe the preparation of a unique new class of STING agonists: isonucleotidic cyclic dinucleotides and the synthesis of their prodrugs. The presented CDNs stimulate STING with comparable efficiency to ADU-S100, whereas their prodrugs demonstrate activity up to four orders of magnitude better due to the improved cellular uptake. The compounds are very potent inducers of inflammatory cytokines by peripheral blood mononuclear cells (PBMCs). We also report the X-ray crystal structure of the lead inhibitor bound to the wild-type (WT) STING.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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