Discovery of Clinical Candidate IAG933, a Potent YAP-TEAD PPI Disrupter

Journal of Medicinal Chemistry 2026

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Authors: Markus Vögtle, Holger Sellner, Emilie A. Chapeau, Pascal Furet, Bahaâ Salem, Mickaël Le Douget, Vincent Bordas, Jean-Marc Groell, Anne-Laure Le Goff, Christine Rouzet, Thomas Wietlisbach, Thomas Zimmermann
+11 more Joseph P. McKenna, Cara E. Brocklehurst, Patrick Chène, Markus Wartmann, Clemens Scheufler, Jörg Kallen, Kanter Ruben de, Stephanie Harlfinger, Frédéric J. Zécri, Tobias Schmelzle, Nicolas Soldermann
DOI: 10.1021/acs.jmedchem.5c03009
Cited by: 4
References: 36

Abstract

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.

Fields of Study & Subjects

Hippo pathway signaling and YAP/TAZ Prostate Cancer Treatment and Research Peptidase Inhibition and Analysis

Publication details

Journal / source
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Volume
69
Issue
7
Pages
7782–7816
Publication date
4 March 2026
Language
EN