Off-target autophagy disruption associated with a novel liver toxicity in dogs for a highly basic heterobifunctional protein degrader
This mechanism is a further demonstration of how the physicochemical properties of bifunctional degraders may challenge preclinical development, and its elucidation provides a path forward for development of degrader compounds with improved toxicity profiles.
Authors
- Lise I. Loberg
- Christopher Untucht (ORCID: https://orcid.org/0009-0009-1111-1869)
- James E. Kath (ORCID: https://orcid.org/0000-0003-3767-9822)
- James W. Sawicki (ORCID: https://orcid.org/0000-0003-3166-6991)
- Alexey Rivkin
- Kenneth P. Robinson
- Rita Ciurlionis
- Jingyi Gong (ORCID: https://orcid.org/0000-0001-7848-1084)
- Rebecca Kohnken (ORCID: https://orcid.org/0000-0003-2323-9180)
- Céline Imhof (ORCID: https://orcid.org/0000-0003-4492-9009)
- Timothy G. Brayman
- Ryan A. McClure (ORCID: https://orcid.org/0000-0002-0163-9290)
- Spencer O. Scholz (ORCID: https://orcid.org/0000-0002-5082-7204)
- Junhai Yang (ORCID: https://orcid.org/0000-0001-6469-2534)
- Christian Pohl
- Zhaozhong J. Jia
- Katharina Haag
- Bo Liu (ORCID: https://orcid.org/0009-0005-6182-8172)
- Alexander Buzenski
- Asra Habibullah
Institutions
- AbbVie (United States) (US)
- Klinikum Ludwigshafen (DE)
Publication Details
- Journal
- Frontiers in Pharmacology
- Published
- 2025-12-10
- DOI
- https://doi.org/10.3389/fphar.2025.1664889
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00