Patent
Cyclic dinucleotides as agonists of stimulator of interferon gene dependent signalling
TLDR
In this article, cyclic dinucleotide compounds and compositions and their application as pharmaceuticals for the treatment of disease are presented and evaluated. But they are not suitable for use as vaccine adjuvants.Abstract:
Disclosed herein are new cyclic dinucleotide compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulation of immune response to disease, and induce Stimulator of Interferon Genes (STING) dependent type I interferon production and co-regulated genes in a human or animal subject are also provided for the treatment diseases such as cancer, particularly metastatic solid tumors and lymphomas, inflammation, allergic and autoimmune disease, infectious disease, and for use as anti-viral agents and vaccine adjuvants.read more
Citations
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Patent
Cyclic di-nucleotide compounds and methods of use
TL;DR: In this article, cyclic-di-nucleotide cGAMP analogs, methods of synthesizing the compounds, pharmaceutical compositions comprising the compounds thereof, and use of compounds and compositions in medical therapy are discussed.
Patent
Compounds, compositions, and methods for the treatment of disease
Radhakrishnan P. Iyer,Seetharamaiyer Padmanabhan,Dillon Cleary,Geeta Meher,Rayomand Gimi,Anjaneyulu Sheri,Shenghua Zhou,Sreerupa Challa +7 more
TL;DR: In this article, the authors describe compounds and compositions for the induction of expression of a pattern recognition receptor (e.g., STING) and methods of use thereof, and propose a method of using STING for pattern recognition.
Journal ArticleDOI
Synthesis and Biological Evaluation of Phosphoester and Phosphorothioate Prodrugs of STING Agonist 3',3'-c-Di(2'F,2'dAMP).
Markéta Pimková Polidarová,Markéta Pimková Polidarová,Petra Břehová,Martin Maxmilian Kaiser,Miroslav Smola,Martin Dračínský,Joshua R. Smith,Aleš Marek,Milan Dejmek,Michal Šála,Ondrej Gutten,Lubomír Rulíšek,Barbora Novotna,Barbora Novotna,Andrea Brázdová,Zlatko Janeba,Radim Nencka,Evzen Boura,Ondřej Páv,Gabriel Birkus +19 more
TL;DR: In this article, the authors evaluate the activity of 3,3'-c-di(2'F,2dAMP) and its phosphorothioate analogues against five STING allelic forms in reporter-cell-based assays and rationalize their findings with X-ray crystallography and quantum mechanics/molecular mechanics calculations.
Patent
Conjugates and methods of use thereof for selective delivery of immune-modulatory agents
TL;DR: In this article, the compositions of conjugates comprising immune-modulatory agents are also provided, including methods for treating disorders, such as cancer and fibrosis, as well as methods of preparation and use of the conjugate.
Journal ArticleDOI
STING Activation and its Application in Immuno-Oncology
TL;DR: The cGAS-STING pathway and STing agonists that are in the clinical and preclinical studies are reviewed, recently disclosed patent applications and published journal articles in the field are summarized and both cyclic dinucleotide analogs and non-nucleic acid derived STING agonists are covered.
References
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Journal ArticleDOI
STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade
Juan Fu,David B. Kanne,Meredith L. Leong,Laura Hix Glickman,Sarah M. McWhirter,Edward E. Lemmens,Ken Mechette,Justin Leong,Peter Lauer,Weiqun Liu,Kelsey E. Sivick,Qi Zeng,Kevin C. Soares,Lei Zheng,Daniel A. Portnoy,Joshua J. Woodward,Drew M. Pardoll,Thomas W. Dubensky,Young J. Kim +18 more
TL;DR: The authors modified the cyclic dinucleotides to strengthen their binding to human STING, increasing their antitumor activity and showed that treatment with STINGVAX caused cancer cells to up-regulate PD-L1, a protein that suppresses the immune response.
Journal ArticleDOI
The host STING pathway at the interface of cancer and immunity
TL;DR: Analysis of the biology of this natural immune response has revealed a major role for the stimulator of IFN genes pathway (STING pathway), which senses cytosolic tumor-derived DNA within the cytosol of tumor-infiltrating DCs.
Patent
Compositions and methods for activating "stimulator of interferon gene"-dependent signalling
Thomas W. Dubensky,David B. Kanne,Meredith Lai Ling Leong,Laura Hix Glickman,Russell E. Vance,Edward Emile Lemmens +5 more
TL;DR: In this article, a cyclic-di-nucleotide (CDN) immune stimulator that activate DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes).
Patent
Cyclic di-nucleotide compounds as sting agonists
Michael D. Altman,Brian M. Andresen,Wonsuk Chang,Matthew Lloyd Childers,Jared N. Cumming,Andrew M. Haidle,Timothy J. Henderson,James P. Jewell,Rui Liang,Jongwon Lim,Hong Liu,Min Lu,Alan B. Northrup,Ryan D. Otte,Tony Siu,Benjamin Wesley Trotter,Quang T. Truong,Shawn P. Walsh,Kake Zhao +18 more
TL;DR: In this article, a class of polycyclic compounds of general formula (II), of general form (II'), or of general condition (II) was defined, which may be useful as inductors of type I interferon production, specifically as STING active agents.
Patent
Compositions comprising cyclic purine dinucleotides having defined stereochemistries and methods for their preparation and use
Thomas W. Dubensky,David B. Kanne,Leong Meredith Lai Ling,Edward E. Lemmens,Glickman Laura Hix +4 more
TL;DR: In this paper, a cyclic-di-nucleotide (CDN) immune stimulator that activates DCs via a recently discovered cytoplasmic receptor known as STING (Stimulator of Interferon Genes).