6VKE
Crystal Structure of Inhibitor JNJ-40012665 in Complex with Prefusion RSV F Glycoprotein
Summary for 6VKE
| Entry DOI | 10.2210/pdb6vke/pdb |
| Descriptor | Prefusion RSV F (DS-Cav1), 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, 4-(5-chloro-2-{[1-(3,4-dimethoxyphenyl)-2-oxo-1,2-dihydro-3H-imidazo[4,5-c]pyridin-3-yl]methyl}-1H-indol-1-yl)butanenitrile, ... (6 entities in total) |
| Functional Keywords | inhibitor, complex, viral protein |
| Biological source | Human respiratory syncytial virus More |
| Total number of polymer chains | 1 |
| Total formula weight | 64382.76 |
| Authors | McLellan, J.S. (deposition date: 2020-01-20, release date: 2020-05-27, Last modification date: 2024-11-20) |
| Primary citation | 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 Cited by 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: 32407115DOI: 10.1021/acs.jmedchem.0c00226 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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