7SSM

Crystal structure of human STING R232 in complex with compound 11

7SSM の概要

• エントリーDOI: 10.2210/pdb7ssm/pdb
• 分子名称: 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)
• 機能のキーワード: receptor, 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: 24390.25

構造登録者

Sack, J.S.,Critton, D.A. (登録日: 2021-11-11, 公開日: 2022-02-09, 最終更新日: 2023-10-18)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.96 Å)