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An orally available non-nucleotide STING agonist with antitumor activity
Abstract
Targeting STING for cancer therapy: Activation of the STING (stimulator of interferon genes) protein by cyclic dinucleotide metabolites plays a critical role in antitumor immunity. The development of synthetic STING agonists is therefore being pursued as a strategy for cancer therapy, but the inherent instability of dinucleotides has limited current efforts. Pan et al. and Chin et al. identified stable STING agonists that act in a “closed” conformation similar to the natural STING ligand, cyclic guanosine monophosphate–adenosine monophosphate (see the Perspective by Gajewski and Higgs). The small molecules can be given orally—an advantage over previously developed STING agonists, which required intratumoral administration. After oral or systemic administration in mice, the agonists activated STING and diverse immune cell types to promote antitumor immunity. These studies represent progress toward clinically viable STING agonists for cancer immunotherapy. Science , this issue p. eaba6098 , p. 993 ; see also p. 921
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“Recently, some novel STING agonists such as diABZI and MSA-2 have been developed which could be systemically administrated [268, 269].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [269]
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Metadata
- Authors
- Pan, B.-S., Perera, S. A., Piesvaux, J. A., Presland, J. P., Schroeder, G. K., Cumming, J. N., Trotter, B. W., Altman, M. D., Buevich, A. V., Cash, B., Cemerski, S., Chang, W., Chen, Y., Dandliker, P. J., Feng, G., Haidle, A., Henderson, T., Jewell, J., Kariv, I., Knemeyer, I., Kopinja, J., Lacey, B. M., Laskey, J., Lesburg, C. A., Liang, R., Long, B. J., Lu, M., Ma, Y., Minnihan, E. C., O’Donnell, G., Otte, R., Price, L., Rakhilina, L., Sauvagnat, B., Sharma, S., Tyagarajan, S., Woo, H., Wyss, D. F., Xu, S., Bennett, D. J., & Addona, G. H.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Department of Discovery Oncology, Merck & Co., Inc., Kenilworth, NJ, USA.
- Department of Quantitative Biosciences, Merck & Co., Inc., Kenilworth, NJ, USA.
- Corresponding author
- Pan, Bo-Sheng
- Perera, Samanthi A.
- Piesvaux, Jennifer A.
- Presland, Jeremy P.
- Schroeder, Gottfried K.
- Cumming, Jared N.
- Trotter, B. Wesley
- Bennett, David Jonathan
- Addona, George H.
- ORCID
- Pan, Bo-Sheng
- Perera, Samanthi A.
- Piesvaux, Jennifer A.
- Presland, Jeremy P.
- Schroeder, Gottfried K.
- Cumming, Jared N.
- Trotter, B. Wesley
- Buevich, Alexei V.
- Cash, Brandon
- Cemerski, Saso
- Chang, Wonsuk
- Chen, Yiping
- Dandliker, Peter J.
- Feng, Guo
- Haidle, Andrew
- Kariv, Ilona
- Knemeyer, Ian
- Kopinja, Johnny
- Lacey, Brian M.
- Laskey, Jason
- Lesburg, Charles A.
- Liang, Rui
- Long, Brian J.
- Lu, Min
- Minnihan, Ellen C.
- O’Donnell, Greg
- Otte, Ryan
- Price, Laura
- Rakhilina, Larissa
- Sauvagnat, Berengere
- Sharma, Sharad
- Tyagarajan, Sriram
- Woo, Hyun
- Wyss, Daniel F.
- Bennett, David Jonathan
- Addona, George H.
- Venue
- Science
- Published
- 2020-08-21
- Volume
- 369
- Issue
- 6506
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3061136593
- Cited by
- 694
- References
- 36
- Citations by year
- 2026: 127 · 2025: 159 · 2024: 124 · 2023: 107 · 2022: 102 · 2021: 61 · 2020: 14
- FWCI
- 25.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- STING agonist, MSA-2, oral drug delivery, innate immunity, antitumor immunity, interferon-beta, anti-PD-1 combination therapy, covalent dimers, tumor microenvironment acidification, cancer immunotherapy
- MeSH terms
- STING Protein, Administration, Oral, Animals, Antineoplastic Agents, Humans, Membrane Proteins
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