ISDA: 9SYN

Deposition Date 2025-10-13

Release Date 2026-03-11

Last Version Date 2026-04-22

Entry Detail

PDB ID:

9SYN

Keywords:

TRANSCRIPTION

Title:

Crystal structure of TEAD4 in complex with Vgll1-peptide and IAG933

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)
Mus musculus (Taxon ID: 10090)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.30 Å

R-Value Free:

0.23

R-Value Work:

0.20

R-Value Observed:

0.20

Space Group:

P 21 21 21

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Transcriptional enhancer fact
Gene (Uniprot):TEAD4
Chain IDs:A
Chain Length:220
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:Q15561 Pfam ID:PF17725

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Transcription cofactor vestig
Gene (Uniprot):Vgll1
Chain IDs:B
Chain Length:18
Number of Molecules:1
Biological Source:Mus musculus

UniProt ID:Q99NC0 Pfam ID:PF07545

Ligand Molecules

MYR

WCF

Primary Citation

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

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.Show

J. Med. Chem. 69 7782 7816 (2026)

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

Abstact

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.

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Protein

Chemical

Disease

Primary Citation of related structures

Abstact

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