2. Academic Validation
  3. Discovery and Characterization of GLPG3808, a PAPD5/7 Inhibitor for Suppression of Hepatitis B Viral Infections

Discovery and Characterization of GLPG3808, a PAPD5/7 Inhibitor for Suppression of Hepatitis B Viral Infections

  • J Med Chem. 2026 Feb 12;69(3):2006-2024. doi: 10.1021/acs.jmedchem.5c01703.
Oscar Mammoliti 1,  Adeline Palisse 1,  Ann De Blieck 1,  Caroline Joannesse 1,  Brigitte Allart 1,  Chris Laruelle 1,  Alex Jaunet 1,  Tom De Munck 1,  Steven Van der Plas 1,  Béranger Duthion 2,  Cornel Catana 1,  Thierry Christophe 1,  Nicolas Houvenaghel 1,  Vincent Porte 1,  Juan-Miguel Jimenez 1,  Filip Beirinckx 1,  Annelies Iwens 1,  Melanie Chypre 1,  Kim De Rijck 1,  Nele Vandervoort 1,  Luc Nelles 1,  Philippe Clément-Lacroix 2,  Carole Delachaume 2,  Cécile Belleville 2,  Line Oste 1,  Monica Borgonovi 2,  Emanuelle Wakselman 2,  Mia Jans 1,  Josee Hue-Perron 2,  Laurent Saniere 2,  Reginald Brys 1,  Martin Andrews 1
Affiliations

Affiliations

  • 1 Galapagos NV, Generaal De Wittelaan L11 A3, 2800 Mechelen, Belgium.
  • 2 Galapagos SASU, 102 avenue Gaston Roussel, 93230 Romainville, France.
PMID: 41557942 DOI: 10.1021/acs.jmedchem.5c01703
Abstract

Hepatitis B virus (HBV) is the most common and severe liver Infection, and approximately 260 million people suffer from chronic hepatitis B Infection, which can lead to life-threatening conditions such as cirrhosis and hepatocellular carcinoma. Treatment of the Infection resulting in sustained clearance of hepatitis B surface antigen (HBsAg) is considered as "functional cure". Although current treatments effectively reduce the viral load, few agents have achieved HBsAg reduction. In this context, we focused on PAPD5/7 inhibitors as effective HBsAg suppressors. Leveraging a 2-oxo-5H-chromeno[4,3-b]pyridine template, we exploited a chemical enablement strategy for broad combinatorial explorations. This rapidly led to the identification of optimal groups not seen in Other PAPD5/7 inhibitors. The effort culminated with the extremely potent preclinical candidate GLPG3808, which was active in an animal model of HBV Infection. Progression was halted after neurological findings in a 13-week toxicological study in rat.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-181347
    PAPD5/PAPD7 Inhibitor
    HBV