9FZA
TEAD1/YAP in complex with a reversible inhibitor N-[(4-phenoxyphenyl)methyl]imidazo[1,2-a]pyridine-3-carboxamide
This is a non-PDB format compatible entry.
Summary for 9FZA
| Entry DOI | 10.2210/pdb9fza/pdb |
| Descriptor | Transcriptional enhancer factor TEF-1, Transcriptional coactivator YAP1, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | irreversible covalent inhibitor, mesothelioma tumor regression, transcription, transcription regulation, transcription-protein binding complex |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 65120.86 |
| Authors | Musil, D.,Freire, F. (deposition date: 2024-07-04, release date: 2024-10-16, Last modification date: 2024-11-06) |
| Primary citation | Carswell, E.,Heinrich, T.,Petersson, C.,Gunera, J.,Garg, S.,Schwarz, D.,Schlesiger, S.,Fischer, F.,Eichhorn, T.,Calder, M.,Smith, G.,MacDonald, E.,Wilson, H.,Hazel, K.,Trivier, E.,Broome, R.,Balsiger, A.,Sirohi, S.,Musil, D.,Freire, F.,Schilke, H.,Dillon, C.,Wienke, D. Discovery of reversible and covalent TEAD 1 selective inhibitors MSC-1254 and MSC-5046 based on one scaffold. Bioorg.Med.Chem.Lett., 114:129981-129981, 2024 Cited by PubMed Abstract: The Transcriptional Enhanced Associated Domain (TEAD) family of transcription factors are key components of the Hippo signalling family which play a crucial role in the regulation of cell proliferation, differentiation and apoptosis. The identification of inhibitors of the TEAD transcription factors are an attractive strategy for the development of novel anticancer therapies. A HTS campaign identified hit 1, which was optimised using structure-based drug design, to deliver potent TEAD1 selective inhibitors with both a reversible and covalent mode of inhibition. The preference for TEAD1 could be rationalised by steric differences observed in the lower pocket of the palmitoylation-site between subtypes, with TEAD1 having the largest available volume to accommodate substitution in this region. PubMed: 39369801DOI: 10.1016/j.bmcl.2024.129981 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.214 Å) |
Structure validation
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