4EEH
Hsp90 Alpha N-terminal Domain in Complex with an Inhibitor 3-(4-Hydroxy-phenyl)-1H-indazol-6-ol
Summary for 4EEH
| Entry DOI | 10.2210/pdb4eeh/pdb |
| Related | 3B28 4EFT 4EFU |
| Descriptor | Heat shock protein HSP 90-alpha, 3-(4-hydroxyphenyl)-1H-indazol-6-ol, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | atp binding, chaperone-chaperone inhibitor complex, chaperone/chaperone inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P07900 |
| Total number of polymer chains | 1 |
| Total formula weight | 26036.12 |
| Authors | Musil, D.,Lehmann, M.,Graedler, U.,Buchstaller, H.-P. (deposition date: 2012-03-28, release date: 2012-06-27, Last modification date: 2024-03-20) |
| Primary citation | Buchstaller, H.-P.,Eggenweiler, H.-M.,Sirrenberg, C.,Graedler, U.,Musil, D.,Hoppe, E.,Zimmermann, A.,Schwartz, H.,Maerz, J.,Bomke, J.,Wegener, A.,Wolf, M. Fragment-based discovery of hydroxy-indazole-carboxamides as novel small molecule inhibitors of Hsp90 Bioorg.Med.Chem.Lett., 22:4396-4403, 2012 Cited by PubMed Abstract: Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential molecular therapeutic agents for the treatment of cancer. Here we describe the identification of novel small molecular weight inhibitors of Hsp90 using a fragment based approach. Fragments were selected by docking, tested in a biochemical assay and the confirmed hits were crystallized. Information gained from X-ray structures of these fragments and other chemotypes was used to drive the fragment evolution process. Optimization of these high μM binders resulted in 3-benzylindazole derivatives with significantly improved affinity and anti-proliferative effects in different human cancer cell lines. PubMed: 22632933DOI: 10.1016/j.bmcl.2012.04.121 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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