9SYI

Crystal structure of TEAD4 in complex with compound 9

This is a non-PDB format compatible entry.

Summary for 9SYI

• Entry DOI: 10.2210/pdb9syi/pdb
• Descriptor: Transcriptional enhancer factor TEF-3, (2~{R})-2-[2-chloranyl-5-[2-chloranyl-4-(trifluoromethyl)phenoxy]phenyl]sulfanylpropanoic acid, 2-[(2~{S})-5-chloranyl-2-phenyl-2-[(2~{S})-pyrrolidin-2-yl]-3~{H}-1-benzofuran-4-yl]-3-fluoranyl-4-methoxy-benzamide, ... (5 entities in total)
• Functional Keywords: inhibitor, complex, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 53141.93

Authors

Scheufler, C.,Izaac, A. (deposition date: 2025-10-13, release date: 2026-03-11)

Primary citation

Vogtle, M.,Sellner, H.,Chapeau, E.,Furet, P.,Salem, B.,Le Douget, M.,Bordas, V.,Groell, J.M.,Le Goff, A.L.,Rouzet, C.,Wietlisbach, T.,Zimmermann, T.,McKenna, J.,Brocklehurst, C.E.,Chene, P.,Wartmann, M.,Scheufler, C.,Kallen, J.,de Kanter, R.,Harlfinger, S.,Zecri, F.,Schmelzle, T.,Soldermann, N.
Discovery of Clinical Candidate IAG933, a Potent YAP-TEAD PPI Disrupter.
J.Med.Chem., 2026

PubMed 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.

PubMed: 41780024
DOI: 10.1021/acs.jmedchem.5c03009

Experimental method

X-RAY DIFFRACTION (2.102 Å)