| Autor: |
Kesteleyn, Bart, Bonfanti, Jean-François, Bardiot, Dorothée, De Boeck, Benoît, Goethals, Olivia, Kaptein, Suzanne J. F., Stoops, Bart, Coesemans, Erwin, Fortin, Jérôme, Muller, Philippe, Doublet, Frédéric, Carlens, Gunter, Koukni, Mohamed, Smets, Wim, Raboisson, Pierre, Chaltin, Patrick, Simmen, Kenny, Loock, Marnix Van, Neyts, Johan, Marchand, Arnaud, Jonckers, Tim H. M. |
| Zdroj: |
Journal of Medicinal Chemistry; March 2024, Vol. 67 Issue: 5 p4063-4082, 20p |
| Abstrakt: |
Dengue is a global public health threat, with about half of the world’s population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no dengue-specific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of JNJ-1802as a potent, pan-serotype DENV inhibitor (EC50’s ranging from 0.057 to 11 nM against the four DENV serotypes). The observed oral bioavailability of JNJ-1802across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a dose-proportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802is being progressed in clinical studies for the prevention or treatment of dengue. |
| Databáze: |
Supplemental Index |
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