7KVX

Structure of hSTING in complex with novel carbocyclic pyrimidine CDN 1

7KVX の概要

• エントリーDOI: 10.2210/pdb7kvx/pdb
• 分子名称: Stimulator of interferon genes protein, (2R,5R,7R,8R,10R,12aR,14R,15aS,16R)-7-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-16-hydroxy-14-[(pyrimidin-4-yl)amino]-2,10-disulfanyldecahydro-2H,10H-5,8-methano-2lambda~5~,10lambda~5~-cyclopenta[l][1,3,6,9,11,2,10]pentaoxadiphosphacyclotetradecine-2,10-dione (3 entities in total)
• 機能のキーワード: immunotherapy, stimulator of interferon genes, cyclic dinucleotide, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27860.16

構造登録者

Skene, R. (登録日: 2020-11-29, 公開日: 2021-06-02, 最終更新日: 2023-10-18)

主引用文献

Vyskocil, S.,Cardin, D.,Ciavarri, J.,Conlon, J.,Cullis, C.,England, D.,Gershman, R.,Gigstad, K.,Gipson, K.,Gould, A.,Greenspan, P.,Griffin, R.,Gulavita, N.,Harrison, S.,Hu, Z.,Hu, Y.,Hata, A.,Huang, J.,Huang, S.C.,Janowick, D.,Jones, M.,Kolev, V.,Langston, S.P.,Lee, H.M.,Li, G.,Lok, D.,Ma, L.,Mai, D.,Malley, J.,Matsuda, A.,Mizutani, H.,Mizutani, M.,Molchanova, N.,Nunes, E.,Pusalkar, S.,Renou, C.,Rowland, S.,Sato, Y.,Shaw, M.,Shen, L.,Shi, Z.,Skene, R.,Soucy, F.,Stroud, S.,Xu, H.,Xu, T.,Abu-Yousif, A.O.,Zhang, J.
Identification of Novel Carbocyclic Pyrimidine Cyclic Dinucleotide STING Agonists for Antitumor Immunotherapy Using Systemic Intravenous Route.
J.Med.Chem., 64:6902-6923, 2021

PubMed Abstract: Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferon production upon infection with intracellular pathogens. STING activation can promote increased T-cell activation and inflammation in the tumor microenvironment, resulting in antitumor immunity. Natural and synthetic cyclic dinucleotides (CDNs) are known to activate STING, and several synthetic CDN molecules are being investigated in the clinic using an intratumoral administration route. Here, we describe the identification of STING agonist , a cyclic dinucleotide structurally diversified from natural ligands with optimized properties for systemic intravenous (iv) administration. Our studies have shown that STING activation by leads to an acute innate immune response as measured by cytokine secretion and adaptive immune response via activation of CD8+ cytotoxic T-cells, which ultimately provides robust antitumor efficacy.

PubMed: 34000802
DOI: 10.1021/acs.jmedchem.1c00374

実験手法

X-RAY DIFFRACTION (2.48 Å)