9S6M
Structure of BFL1 in complex with a covalent inhibitor, alternative series, cmpd25
This is a non-PDB format compatible entry.
Summary for 9S6M
| Entry DOI | 10.2210/pdb9s6m/pdb |
| Descriptor | Bcl-2-related protein A1, (1~{R},2~{R})-2-azanyl-~{N}-[4-[(1~{R})-1-[propanoyl-[4-(trifluoromethyloxy)phenyl]amino]ethyl]phenyl]cyclopentane-1-carboxamide (3 entities in total) |
| Functional Keywords | bfl1, covalent, inhibitor, apoptosis |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 35812.76 |
| Authors | Cottee, M.A.,Hargreaves, D. (deposition date: 2025-08-01, release date: 2026-01-14, Last modification date: 2026-01-28) |
| Primary citation | Blackwell, J.H.,Lucas, S.C.C.,Battocchio, G.,Borjesson, U.,Bostock, M.J.,Braybrooke, E.L.,Cheung, T.,Cottee, M.A.,Beaumont, K.C.,Gohlke, A.,Hargreaves, D.,van Hoek-Emmelot, M.,van Hoeven, V.,Jansen, C.,Kawatkar, A.,Kinzel, O.,Kumar, P.,Kupcova, L.,Lainchbury, M.D.,Leon, L.,Milbradt, A.G.,Palisse, A.,Schade, M.,van Rijbroek, K.,Sacchetto, C.,Schellekens, R.,Su, N.,Xu, H.,Zhao, H.,Chen, Y.,Huang, S. Optimization and Chemoproteomic Profiling of a Selective, Covalent Bfl-1-Targeting Cellular Tool. J.Med.Chem., 69:1218-1246, 2026 Cited by PubMed Abstract: We describe herein the discovery and optimization of a potent and irreversible cellular probe for selective labeling of , a member of the . This chemical series demonstrates robust selectivity for Bfl-1 over other related antiapoptotic proteins and exhibits favorable cellular potency as well as promising pharmacokinetics. Notably, compound achieves a / value of and elicits caspase activation at submicromolar concentrations in cellular assays. To comprehensively profile proteome-wide selectivity, we performed chemoproteomic analyses on compound alongside our previously reported Bfl-1 inhibitors. This enabled critical insights into potential off-target interactions and facilitated direct comparison of off-target profiles among distinct chemotypes targeting Bfl-1. PubMed: 41432228DOI: 10.1021/acs.jmedchem.5c02581 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.427 Å) |
Structure validation
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