6VKD

Crystal Structure of Inhibitor JNJ-36689282 in Complex with Prefusion RSV F Glycoprotein

6VKD の概要

• エントリーDOI: 10.2210/pdb6vkd/pdb
• 分子名称: Prefusion RSV F (DS-Cav1), 1-cyclopropyl-3-({1-[3-(methylsulfonyl)propyl]-1H-pyrrolo[3,2-c]pyridin-2-yl}methyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, viral protein
• 由来する生物種: Human respiratory syncytial virus; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64255.68

構造登録者

McLellan, J.S. (登録日: 2020-01-20, 公開日: 2020-05-27, 最終更新日: 2024-10-23)

主引用文献

Vendeville, S.,Tahri, A.,Hu, L.,Demin, S.,Cooymans, L.,Vos, A.,Kwanten, L.,Van den Berg, J.,Battles, M.B.,McLellan, J.S.,Koul, A.,Raboisson, P.,Roymans, D.,Jonckers, T.H.M.
Discovery of 3-({5-Chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus.
J.Med.Chem., 63:8046-8058, 2020

PubMed Abstract: Respiratory syncytial virus (RSV) is a seasonal virus that infects the lungs and airways of 64 million children and adults every year. It is a major cause of acute lower respiratory tract infection and is associated with significant morbidity and mortality. Despite the large medical and economic burden, treatment options for RSV-associated bronchiolitis and pneumonia are limited and mainly consist of supportive care. This publication covers the medicinal chemistry efforts resulting in the identification of JNJ-53718678, an orally bioavailable RSV inhibitor that was shown to be efficacious in a phase 2a challenge study in healthy adult subjects and that is currently being evaluated in hospitalized infants and adults. Cocrystal structures of several new derivatives helped in rationalizing some of the structure-activity relationship (SAR) trends observed.

PubMed: 32407115
DOI: 10.1021/acs.jmedchem.0c00226

実験手法

X-RAY DIFFRACTION (2.5 Å)