7Q7U
Crystal structure of human BCL6 BTB domain in complex with compound 9a
Summary for 7Q7U
| Entry DOI | 10.2210/pdb7q7u/pdb |
| Descriptor | B-cell lymphoma 6 protein, 2-chloranyl-4-[[(2S)-2,7-dimethyl-6-oxidanylidene-1,2,3,4-tetrahydro-[1,4]oxazepino[2,3-c]quinolin-10-yl]amino]pyridine-3-carbonitrile (3 entities in total) |
| Functional Keywords | transcription, inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16894.80 |
| Authors | Le Bihan, Y.-V.,van Montfort, R.L.M. (deposition date: 2021-11-09, release date: 2022-06-15, Last modification date: 2024-01-31) |
| Primary citation | Davis, O.A.,Cheung, K.J.,Brennan, A.,Lloyd, M.G.,Rodrigues, M.J.,Pierrat, O.A.,Collie, G.W.,Le Bihan, Y.V.,Huckvale, R.,Harnden, A.C.,Varela, A.,Bright, M.D.,Eve, P.,Hayes, A.,Henley, A.T.,Carter, M.D.,McAndrew, P.C.,Talbot, R.,Burke, R.,van Montfort, R.L.M.,Raynaud, F.I.,Rossanese, O.W.,Meniconi, M.,Bellenie, B.R.,Hoelder, S. Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors. J.Med.Chem., 65:8169-8190, 2022 Cited by PubMed Abstract: To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on attaining close shape complementarity by ring fusion onto our quinolinone lead series. Following exploration of different sized rings, we identified a conformationally restricted core which optimally filled the available space, leading to potent BCL6 inhibitors. Through X-ray structure-guided design, combined with efficient synthetic chemistry to make the resulting novel core structures, a >300-fold improvement in activity was obtained by the addition of seven heavy atoms. PubMed: 35657291DOI: 10.1021/acs.jmedchem.1c02174 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.78 Å) |
Structure validation
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