7B1T
Crystal structure of BRD4(1) in complex with the inhibitor MPM6
Summary for 7B1T
| Entry DOI | 10.2210/pdb7b1t/pdb |
| Descriptor | Bromodomain-containing protein 4, 3-(5-azanyl-2-chloranyl-phenyl)-1-methyl-4,7-dihydro-2~{H}-cyclohepta[c]pyrrol-8-one, DIMETHYL SULFOXIDE, ... (4 entities in total) |
| Functional Keywords | brd4, brd4(1), bet, mpm6, bromodomain, inhibitor, co-crystal, cocrystal, fragment, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15542.40 |
| Authors | Huegle, M. (deposition date: 2020-11-25, release date: 2022-06-08, Last modification date: 2024-02-07) |
| Primary citation | Warstat, R.,Pervaiz, M.,Regenass, P.,Amann, M.,Schmidtkunz, K.,Einsle, O.,Jung, M.,Breit, B.,Hugle, M.,Gunther, S. A novel pan-selective bromodomain inhibitor for epigenetic drug design. Eur.J.Med.Chem., 249:115139-115139, 2023 Cited by PubMed Abstract: For a long time, the development of bromodomain (BD) inhibitors (BDi) was almost exclusively related to the BET family. More recently, BDi for BDs outside the BET family have also been developed. Here we present a novel pan-BDi with micromolar affinities to various BDs, and nanomolar affinities to representatives of BD families I, II (Bromodomain and Extra-Terminal Domain (BET) family), III, and IV. The inhibitor shows a broad activity profile with nanomolar growth inhibition (GI50) values on various cancer cell lines. Subsequently, we were able to control the selectivity of the inhibitor by simple modifications and turned it into a highly selective BRD9 inhibitor. PubMed: 36736153DOI: 10.1016/j.ejmech.2023.115139 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
Download full validation report
