Discovery of Clinical Candidate IAG933, a Potent YAP-TEAD PPI Disrupter
The interaction of transcriptional enhanced associate domain (TEAD) and transcriptional coactivator yes-associated protein (YAP) mediates oncogenic functions downstream of the Hippo pathway. In this report, we outline our efforts to find a potent inhibitor of this protein-protein interaction with suitable properties for clinical evaluation. We detail the medicinal chemistry program that led to the discovery of IAG933, an inhibitor with a balanced ADME profile, enabling its evaluation as a potential treatment option in clinical settings.
Authors
- Clemens Scheufler (ORCID: https://orcid.org/0000-0002-3693-3529)
- Jörg Kallen
- Thomas Wietlisbach
- Markus Wartmann (ORCID: https://orcid.org/0009-0007-9822-3112)
- Mickaël Le Douget
- Vincent Bordas
- Nicolas Soldermann (ORCID: https://orcid.org/0000-0001-8937-9843)
- Frédéric J. Zécri (ORCID: https://orcid.org/0000-0002-2469-8875)
- Kanter Ruben de
- Thomas Zimmermann (ORCID: https://orcid.org/0000-0003-4905-1469)
- Christine Rouzet
- Cara E. Brocklehurst (ORCID: https://orcid.org/0000-0002-0484-5540)
- Holger Sellner (ORCID: https://orcid.org/0000-0002-1052-2043)
- Emilie A. Chapeau (ORCID: https://orcid.org/0000-0002-5563-3951)
- Bahaâ Salem
- Stephanie Harlfinger
- Joseph P. McKenna
- Markus Vögtle
- Anne-Laure Le Goff
- Jean-Marc Groell
- Patrick Chène
- Pascal Furet
- Tobias Schmelzle
Institutions
- Novartis (China) (CN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2026-03-04
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c03009
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 0.00