Front Cover: E7766, a Macrocycle‐Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan‐Genotypic Activity (ChemMedChem 11/2021). (7th June 2021)

• Record Type: Journal Article
• Authors: Kim, Dae‐Shik; Endo, Atsushi; Fang, Francis G.; Huang, Kuan‐Chun; Bao, Xingfeng; Choi, Hyeong‐wook; Majumder, Utpal; Shen, Young Y.; Mathieu, Steven; Zhu, Xiaojie; Sanders, Kristen; Noland, Thomas; Hao, Ming‐Hong; Chen, Yu; Wang, John Y.; Yasui, So; TenDyke, Karen; Wu, Jiayi; Ingersoll, Christy; Loiacono, Kara A.; Hutz, Janna E.; Sarwar, Nadeem
• Is Part Of: ChemMedChem. Volume 16:Number 11(2021)
• Page Start: 1681
• Page End: 1681
• Publication Date: 2021-06-07
• Subjects: cyclic dinucleotides -- drug design -- immuno-oncology -- macrocycles -- STING agonists; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100346
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The Front Cover shows a design concept of STING agonist E7766, locking a STING‐active conformation of cyclic dinucleotides by forming a bridged macrocycle. The conformational rigidity of E7766 and the entropic advantage upon binding to STING led to enhanced potency, stability, and pan‐genotypic activity. Structures of 2'‐fluoro‐2'‐deoxyadenosine monomer, E7766 and E7766‐STING REF co‐crystal are shown on the left, middle, and right locks respectively. The artwork was created by modification of a photo by Masahiro Onoguchi on Unsplash. More information can be found in the Communication by Dae‐Shik Kim et al .