2. Academic Validation
  3. Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor

Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor

  • J Med Chem. 2024 Mar 14;67(5):4063-4082. doi: 10.1021/acs.jmedchem.3c02336.
Bart Kesteleyn 1,  Jean-François Bonfanti 2,  Dorothée Bardiot 3,  Benoît De Boeck 1,  Olivia Goethals 4,  Suzanne J F Kaptein 5,  Bart Stoops 1,  Erwin Coesemans 1,  Jérôme Fortin 2,  Philippe Muller 2,  Frédéric Doublet 2,  Gunter Carlens 3,  Mohamed Koukni 3,  Wim Smets 3,  Pierre Raboisson 1,  Patrick Chaltin 3 6,  Kenny Simmen 1,  Marnix Van Loock 4,  Johan Neyts 5 7,  Arnaud Marchand 3,  Tim H M Jonckers 1
Affiliations

Affiliations

  • 1 Janssen Research & Development, Janssen Pharmaceutica NV, Turnhoutseweg 30, Beerse 2340, Belgium.
  • 2 Janssen Infectious Diseases Discovery, Janssen-Cilag, Chaussée du Vexin, Val de Reuil 27106, France.
  • 3 CISTIM Leuven vzw, Bioincubator 2, Gaston Geenslaan 2, Leuven 3001, Belgium.
  • 4 Janssen Global Public Health R&D, Janssen Pharmaceutica NV, Turnhoutseweg 30, Beerse 2340, Belgium.
  • 5 KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, Leuven 3000, Belgium.
  • 6 Centre for Drug Design and Discovery (CD3), KU Leuven, Bioincubator 2, Gaston Geenslaan 2, Leuven 3000, Belgium.
  • 7 Global Virus Network (GVN), Baltimore, Maryland 21201, United States.
PMID: 38482827 DOI: 10.1021/acs.jmedchem.3c02336
Abstract

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-1802 as 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-1802 across 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-1802 is being progressed in clinical studies for the prevention or treatment of dengue.

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