6QXU
Human TNKS1 in complex with 6,8-Difluoro-2-[4-(1-hydroxy-1-methyl-ethyl)-phenyl]-3H-quinazolin-4-one
Summary for 6QXU
| Entry DOI | 10.2210/pdb6qxu/pdb |
| Descriptor | Poly [ADP-ribose] polymerase tankyrase-1, BETA-MERCAPTOETHANOL, 6,8-bis(fluoranyl)-2-[4-(2-oxidanylpropan-2-yl)phenyl]-3~{H}-quinazolin-4-one, ... (5 entities in total) |
| Functional Keywords | tankyrase, parp, inhibitor, transferase-transferase inhibitor complex, transferase, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 24672.30 |
| Authors | Musil, D.,Lehmann, D.,Buchstaller, H.-P. (deposition date: 2019-03-08, release date: 2019-08-14, Last modification date: 2024-05-01) |
| Primary citation | Buchstaller, H.P.,Anlauf, U.,Dorsch, D.,Kuhn, D.,Lehmann, M.,Leuthner, B.,Musil, D.,Radtki, D.,Ritzert, C.,Rohdich, F.,Schneider, R.,Esdar, C. Discovery and Optimization of 2-Arylquinazolin-4-ones into a Potent and Selective Tankyrase Inhibitor Modulating Wnt Pathway Activity. J.Med.Chem., 62:7897-7909, 2019 Cited by PubMed Abstract: Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological targets that recently gained interest for anticancer therapy in Wnt pathway dependent tumors. 2-Aryl-quinazolinones were identified and optimized into potent tankyrase inhibitors through SAR exploration around the quinazolinone core and the 4'-position of the phenyl residue. These efforts were supported by analysis of TNKS X-ray and WaterMap structures and resulted in compound , a potent, selective tankyrase inhibitor with favorable pharmacokinetic properties. The X-ray structure of in complex with TNKS1 was solved and confirmed the design hypothesis. Modulation of Wnt pathway activity was demonstrated with this compound in a colorectal xenograft model . PubMed: 31381853DOI: 10.1021/acs.jmedchem.9b00656 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
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