7SSM

Crystal structure of human STING R232 in complex with compound 11

Summary for 7SSM

• Entry DOI: 10.2210/pdb7ssm/pdb
• Descriptor: Stimulator of interferon genes protein, 2-({[(8R)-pyrazolo[1,5-a]pyrimidine-3-carbonyl]amino}methyl)-1-benzofuran-7-carboxylic acid (3 entities in total)
• Functional Keywords: receptor, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 24390.25

Authors

Sack, J.S.,Critton, D.A. (deposition date: 2021-11-11, release date: 2022-02-09, Last modification date: 2023-10-18)

Primary citation

Cherney, E.C.,Zhang, L.,Lo, J.,Huynh, T.,Wei, D.,Ahuja, V.,Quesnelle, C.,Schieven, G.L.,Futran, A.,Locke, G.A.,Lin, Z.,Monereau, L.,Chaudhry, C.,Blum, J.,Li, S.,Fereshteh, M.,Li-Wang, B.,Gangwar, S.,Pan, C.,Chong, C.,Zhu, X.,Posy, S.L.,Sack, J.S.,Zhang, P.,Ruzanov, M.,Harner, M.,Akhtar, F.,Schroeder, G.M.,Vite, G.,Fink, B.
Discovery of Non-Nucleotide Small-Molecule STING Agonists via Chemotype Hybridization.
J.Med.Chem., 65:3518-3538, 2022

PubMed Abstract: The identification of agonists of the stimulator of interferon genes (STING) pathway has been an area of intense research due to their potential to enhance innate immune response and tumor immunogenicity in the context of immuno-oncology therapy. Initial efforts to identify STING agonists focused on the modification of 2',3'-cGAMP () (an endogenous STING activator ligand) and other closely related cyclic dinucleotides (CDNs). While these efforts have successfully identified novel CDNs that have progressed into the clinic, their utility is currently limited to patients with solid tumors that STING agonists can be delivered to intratumorally. Herein, we report the discovery of a unique class of non-nucleotide small-molecule STING agonists that demonstrate antitumor activity when dosed intratumorally in a syngeneic mouse model.

PubMed: 35108011
DOI: 10.1021/acs.jmedchem.1c01986

Experimental method

X-RAY DIFFRACTION (1.96 Å)