9QVT
Crystal structure of STING CTD in complex with potent agonist D5
This is a non-PDB format compatible entry.
Summary for 9QVT
| Entry DOI | 10.2210/pdb9qvt/pdb |
| Descriptor | Stimulator of interferon genes protein, 4-[6-methoxy-5-[[6-methoxy-2-(4-oxidanyl-4-oxidanylidene-butanoyl)-1-benzothiophen-5-yl]sulfanylmethylsulfanyl]-1-benzothiophen-2-yl]-4-oxidanylidene-butanoic acid (3 entities in total) |
| Functional Keywords | sting, immune system, cgas, agonist, interferon, signalling, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 27759.30 |
| Authors | dos Reis, C.V.,Hsu, N.-S.,Rooney, T.,Skidmore, J.,Bernardes, G.J.L.,Hyvonen, M. (deposition date: 2025-04-11, release date: 2025-09-24, Last modification date: 2025-12-10) |
| Primary citation | Hsu, N.S.,Tang, C.,Mendes, R.V.,Labao-Almeida, C.,Dos Reis, C.V.,Coelho, A.R.,Marques, M.C.,Cabeza Cabrerizo, M.,Misteli, R.,Rooney, T.P.C.,Hyvonen, M.,Corzana, F.,Fior, R.,Bernardes, G.J.L. Tumour-specific STING agonist synthesis via a two-component prodrug system. Nat.Chem., 17:1941-1951, 2025 Cited by PubMed Abstract: Pharmacological activation of STING holds promise in cancer treatment. A recent trend is the development of tumour-specific or conditionally activated STING agonists for enhanced safety and efficacy. Here we explore an unconventional prodrug activation strategy for on-tumour synthesis of a potent agonist. Leveraging the unique mechanism of MSA2, a small-molecule agonist that dimerizes non-covalently before binding to STING, we showed that its analogues bearing reactive functional groups readily and selectively form covalent dimers under mild conditions and in complex environments. We identified a reacting pair that led to a thioether-linked dimer with submicromolar potency in cell-based assays. Caging one of the reactants with a self-immolative β-glucuronide moiety resulted in a two-component prodrug system that near-exclusively formed the active compounds in tumours overexpressing β-glucuronidase. These results exemplify the use of small-molecule recognition for on-site generation of active compounds from benign precursors. PubMed: 40957952DOI: 10.1038/s41557-025-01930-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.305 Å) |
Structure validation
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