5X9P
Crystal structure of the BCL6 BTB domain in complex with Compound 5
Summary for 5X9P
| Entry DOI | 10.2210/pdb5x9p/pdb |
| Related | 5X9O |
| Descriptor | B-cell lymphoma 6 protein, 3-[[4-chloranyl-2-nitro-5-[(2-oxidanylidene-1,3-dihydrobenzimidazol-5-yl)amino]phenyl]amino]propanoic acid (3 entities in total) |
| Functional Keywords | transcription repressor, transcription-inhibitor complex, transcription/inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus : P41182 |
| Total number of polymer chains | 1 |
| Total formula weight | 16679.50 |
| Authors | Sogabe, S.,Ida, K.,Lane, W.,Snell, G. (deposition date: 2017-03-08, release date: 2017-08-16, Last modification date: 2023-11-22) |
| Primary citation | Yasui, T.,Yamamoto, T.,Sakai, N.,Asano, K.,Takai, T.,Yoshitomi, Y.,Davis, M.,Takagi, T.,Sakamoto, K.,Sogabe, S.,Kamada, Y.,Lane, W.,Snell, G.,Iwata, M.,Goto, M.,Inooka, H.,Sakamoto, J.I.,Nakada, Y.,Imaeda, Y. Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design Bioorg. Med. Chem., 25:4876-4886, 2017 Cited by PubMed Abstract: B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits 1a and 2a, we identified a novel BCL6-corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC=0.10µM, cell-based mammalian two-hybrid [M2H] assay IC=0.72µM) by utilizing structure-based drug design (SBDD) based on an X-ray crystal structure of 1a bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies. PubMed: 28760529DOI: 10.1016/j.bmc.2017.07.037 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.86 Å) |
Structure validation
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