PXD057395 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A Phosphotriester-Masked Dideoxy-cGAMP Derivative as a Cell-Permeable STING Agonist |
Description | 2’3’-cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide second messenger in which guanosine and adenosine are connected by one 3’-5’ and one 2’-5’ phosphodiester linkage. It is formed in the cytosol upon detection of pathogenic DNA by the enzyme guanosine-monophosphate-adenosine monophosphate synthase (cGAS). cGAMP subsequently binds to the adaptor protein stimulator of interferon genes (STING) to elicit an innate immune response leading to the production of type I interferons and cytokines. STING agonists are a highly promising avenue for an immuno-oncological anticancer therapy. A particular challenge with cyclic dinucleotide STING agonists are the two negative charges of the phosphodiester linkages, which strongly reduce the ability of such compounds to penetrate cell membranes. The development of cell-permeable STING agonists that can stimulate the immune system to enhance their anticancer potency is currently of utmost importance in the field. Here, we report the development of a dideoxy derivative of cGAMP as a phosphotriester prodrug, where the negative charge of the phosphate backbone has been masked with a thioester. We found that this thioester-protected compound features a dramatic increase in its cellular potency that rises from EC50 = 5 µM to 25 nM. The new compound is envisioned to enable an efficient STING-agonist-based anticancer therapy. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-07_04:28:54.962.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Markus Müller |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Eclipse; Thermo Fisher Scientific instrument model |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-10-31 07:00:22 | ID requested | |
⏵ 1 | 2025-05-07 04:28:55 | announced | |
Publication List
10.1002/anie.202416353; |
Halbritter AJ, G, ä, rtner YV, Nabiev J, Hernichel F, Ganazzoli G, Ö, zdemir D, Pappa A, Veth S, Stazzoni S, M, ü, ller M, Hornung V, Carell T, A Phosphotriester-Masked Dideoxy-cGAMP Derivative as a Cell-Permeable STING Agonist. Angew Chem Int Ed Engl, 63(52):e202416353(2024) [pubmed] |
Keyword List
submitter keyword: STING, Interferone,cGAMP |
Contact List
Thomas Carell |
contact affiliation | Ludwig-Maximilians Universität München Department Chemie Butenandtstr. 5-13 81377 München |
contact email | thomas.carell@cup.lmu.de |
lab head | |
Markus Müller |
contact affiliation | Ludwig-Maximilians Universität München
Department Chemie
AK Carell
Butenandtstr. 5-13
81377 München |
contact email | markus.mueller@cup.lmu.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057395 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD057395
- Label: PRIDE project
- Name: A Phosphotriester-Masked Dideoxy-cGAMP Derivative as a Cell-Permeable STING Agonist