9FQI
E3 ligase Cbl-b in complex with a lactam scaffold inhibitor (compound 7)
This is a non-PDB format compatible entry.
Summary for 9FQI
| Entry DOI | 10.2210/pdb9fqi/pdb |
| Descriptor | E3 ubiquitin-protein ligase CBL-B, 8-[3-[(4~{R})-4-methyl-2-oxidanylidene-piperidin-4-yl]phenyl]-3-[[(3~{S})-3-methylpiperidin-1-yl]methyl]-5-(trifluoromethyl)-1$l^{4},7,8-triazabicyclo[4.3.0]nona-1(6),2,4-trien-9-one, ZINC ION, ... (5 entities in total) |
| Functional Keywords | ligase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 46465.87 |
| Authors | Schimpl, M. (deposition date: 2024-06-17, release date: 2024-07-31, Last modification date: 2024-09-04) |
| Primary citation | Quinn, T.R.,Giblin, K.A.,Thomson, C.,Boerth, J.A.,Bommakanti, G.,Braybrooke, E.,Chan, C.,Chinn, A.J.,Code, E.,Cui, C.,Fan, Y.,Grimster, N.P.,Kohara, K.,Lamb, M.L.,Ma, L.,Mfuh, A.M.,Robb, G.R.,Robbins, K.J.,Schimpl, M.,Tang, H.,Ware, J.,Wrigley, G.L.,Xue, L.,Zhang, Y.,Zhu, H.,Hughes, S.J. Accelerated Discovery of Carbamate Cbl-b Inhibitors Using Generative AI Models and Structure-Based Drug Design. J.Med.Chem., 67:14210-14233, 2024 Cited by PubMed Abstract: Casitas B-lymphoma proto-oncogene-b (Cbl-b) is a RING finger E3 ligase that has an important role in effector T cell function, acting as a negative regulator of T cell, natural killer (NK) cell, and B cell activation. A discovery effort toward Cbl-b inhibitors was pursued in which a generative AI design engine, REINVENT, was combined with a medicinal chemistry structure-based design to discover novel inhibitors of Cbl-b. Key to the success of this effort was the evolution of the "Design" phase of the Design-Make-Test-Analyze cycle to involve iterative rounds of an in silico structure-based drug design, strongly guided by physics-based affinity prediction and machine learning DMPK predictive models, prior to selection for synthesis. This led to the accelerated discovery of a potent series of carbamate Cbl-b inhibitors. PubMed: 39132828DOI: 10.1021/acs.jmedchem.4c01034 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.954 Å) |
Structure validation
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