7X9Q

Crystal structure of human STING complexed with compound BSP16

Summary for 7X9Q

• Entry DOI: 10.2210/pdb7x9q/pdb
• Descriptor: Stimulator of interferon genes protein, (2R)-4-(5,6-dimethoxy-1-benzoselenophen-2-yl)-2-ethyl-4-oxidanylidene-butanoic acid (3 entities in total)
• Functional Keywords: sting agonists, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 26389.57

Authors

Pan, L.,Guan, X.,Feng, X.,Li, Z.,Bian, J. (deposition date: 2022-03-15, release date: 2022-09-28, Last modification date: 2023-11-29)

Primary citation

Feng, X.,Pan, L.,Qian, Z.,Liu, D.,Guan, X.,Feng, L.,Song, B.,Xu, X.,Tan, N.,Ma, Y.,Li, Z.,Wang, Z.,Bian, J.
Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents.
J.Med.Chem., 65:15048-15065, 2022

PubMed Abstract: Activation of the stimulator of interferon genes (STING) pathway to achieve antitumor response is an attractive approach for cancer immunotherapy. In this study, we report the identification of () as a potent, orally available STING agonist. strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. A 2.4 Å cocrystal structure revealed that could induce the "closed" conformation of STING. studies revealed that is well tolerated, has an excellent pharmacokinetic profile as an oral drug, and induces tumor regression and durable antitumor immunity. The promising bioactivities of make it valuable for further development as an antitumor agent.

PubMed: 36069713
DOI: 10.1021/acs.jmedchem.2c00634

Experimental method

X-RAY DIFFRACTION (2.4 Å)