Structure activity relationship, 6-modified purine riboside analogues to activate hSTING, stimulator of interferon genes

Laurent F. Bonnac; Christine D. Dreis; Robert J. Geraghty

doi:10.1016/j.bmcl.2019.126819

Structure activity relationship, 6-modified purine riboside analogues to activate hSTING, stimulator of interferon genes

Laurent F. Bonnac, Christine D. Dreis, Robert J. Geraghty

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Abstract

Twenty-nine nucleoside analogues have been synthesized and evaluated in a cell based assay for their ability to activate the human Stimulator of Interferon Genes (hSTING), a key protein of the innate immune defense. Some 6-O-alkyl nucleoside analogues activate hSTING without associated cytotoxicity. SAR and combination studies were performed to decipher possible activation mechanism. The described nucleoside hSTING activators represent first-in-class modulators of the innate immune defense; a highly relevant target for antiviral, antibacterial, anticancer or Alzheimer's disease treatments and may present advantages over other types of hSTING activators.

Original language	English (US)
Article number	126819
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2019.126819
State	Published - Jan 15 2020

Bibliographical note

Funding Information:
This research was supported by the Center for Drug Design, College of Pharmacy, University of Minnesota . Appendix A

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

Cell based assay
hSTING activation
Innate immune response
Interferons
Nucleoside analogues

PubMed: MeSH publication types

Journal Article
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10.1016/j.bmcl.2019.126819

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abstract = "Twenty-nine nucleoside analogues have been synthesized and evaluated in a cell based assay for their ability to activate the human Stimulator of Interferon Genes (hSTING), a key protein of the innate immune defense. Some 6-O-alkyl nucleoside analogues activate hSTING without associated cytotoxicity. SAR and combination studies were performed to decipher possible activation mechanism. The described nucleoside hSTING activators represent first-in-class modulators of the innate immune defense; a highly relevant target for antiviral, antibacterial, anticancer or Alzheimer's disease treatments and may present advantages over other types of hSTING activators.",

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AU - Bonnac, Laurent F.

AU - Dreis, Christine D.

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KW - Interferons

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Structure activity relationship, 6-modified purine riboside analogues to activate hSTING, stimulator of interferon genes

Abstract

Bibliographical note

Keywords

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UN SDGs

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