Discovery of AIC263282, a Hepatitis B Virus Capsid Assembly Modulator Ready for Candidate Profiling

  • J Med Chem. 2025 Mar 27;68(6):6361-6371. doi: 10.1021/acs.jmedchem.4c02838.
Bernhard Lesch  1 ,  Alexander Birkmann  1 ,  Susanne Bonsmann  1 ,  Alastair Donald  1 ,  Florian Engel  1 ,  Thomas Goldner  1 ,  Kamal Kumar  1 ,  Tamara Pfaff  1 ,  Andreas Urban  1 ,  Holger Zimmermann  1 ,  Alexandra E Bosnidou  2 ,  Estefanía Del Castillo  2 ,  Félix Cuevas  2 ,  Elena Detta  2 ,  Daniel Font  2 ,  Jordi González García  2 ,  Justine Raymond  1  2 ,  Maria Ángeles Sarmentero  2 ,  Arjen Cnossen  3 ,  Wessel Sinnige  3 ,  Jack C Slootweg  3 ,  Anita Wegert  3 ,  Helmut Buschmann  1
Affiliations
  • 1. AiCuris Anti-infective Cures AG, Friedrich-Ebert-Str.475/Geb.302, 42117 Wuppertal, Germany.
  • 2. Institute of Chemical Research of Catalonia (ICIQ), Barcelona Institute of Science and Technology (BIST), Avgda. Països Catalans 16, 43007 Tarragona, Spain.
  • 3. Symeres, Kerkenbos 1013, 6546 BB Nijmegen, The Netherlands.
PMID: 40103295 DOI: 10.1021/acs.jmedchem.4c02838
Abstract

Hepatitis B Virus (HBV) infections remain a threat to the global public health. Nucleoside analogues remain the mainstay of therapy despite their discouraging cure rates achieved. Capsid assembly modulators (CAMs) have been at the center of HBV research, but despite having shown clinical efficacy on viral load in clinical studies, market entry has been elusive. Herein, we present the optimization program of our lead series. Setting our focus on potency, solubility, and hERG liability, these studies resulted in AIC263282, a new, potent capsid assembly modulator with improved physicochemical properties, which is ready for profiling as a preclinical candidate.

Products