8YMH
BRD4-BD1 in complex with 5-methyl-2-{[(2R)-2-methyl-4-methylsulfonyl-piperazin-1-yl]methyl}-7-(1-methylpyrazol-3-yl)furo[3,2-c]pyridin-4-one
This is a non-PDB format compatible entry.
Summary for 8YMH
| Entry DOI | 10.2210/pdb8ymh/pdb |
| Descriptor | Bromodomain-containing protein 4, 5-methyl-2-{[(2R)-2-methyl-4-methylsulfonyl-piperazin-1-yl]methyl}-7-(1-methylpyrazol-3-yl)furo[3,2-c]pyridin-4-one, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | brd4, epigenetic, signaling protein-inhibitor complex, signaling protein/inhibitor, signaling protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15700.07 |
| Authors | Sasaki, C.,Miyaguchi, I.,Hagihara, S.,Ishizawa, K.,Endo, J. (deposition date: 2024-03-09, release date: 2025-03-12, Last modification date: 2025-12-17) |
| Primary citation | Hagihara, S.,Ishizawa, K.,Kikuchi, M.,Kawano, Y.,Nishidate, A.,Matsumoto, F.,Hashimoto, N.,Sasaki, C.,Miyaguchi, I.,Okada, O.,Akashi, T.,Nakayama, S.,Ogasawara, Y.,Endo, J. Discovery of a potent, orally available furopyridine derivative as a novel selective bromodomain and extra-terminal domain (BET)-first bromodomain (BD1) inhibitor. Bioorg.Med.Chem.Lett., 109:129848-129848, 2024 Cited by PubMed Abstract: We explored novel immunosuppressive agents with immune tolerance using a phenotypic drug discovery strategy, focusing on costimulatory molecules in T cells, and obtained triazolothienodiazepine derivatives. Their mechanism of action is to inhibit the bromodomain and extra-terminal domain (BET) family, as we have previously reported. Selective inhibition of the first bromodomain (BD1) of the BET family is expected to exert antitumor and immunosuppressive effects, similar to BET inhibitors. This study identified furopyridine derivatives 7 and 8 with high BD1 inhibitory activity and high selectivity over BD2. Compound 7 was found to be orally bioavailable and exhibited anti-inflammatory activity in a lipopolysaccharide-induced model. PubMed: 38876176DOI: 10.1016/j.bmcl.2024.129848 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.04 Å) |
Structure validation
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