8BI2
Syk kinase domain in complex with macrocyclic inhibitor 20a
Summary for 8BI2
| Entry DOI | 10.2210/pdb8bi2/pdb |
| Descriptor | Tyrosine-protein kinase SYK, 10,13,23-trimethyl-16-oxa-2,4,8,9,13,19,23,30-octazapentacyclo[19.5.2.1^{3,7}.1^{8,11}.0^{24,28}]triaconta-1(27),3,5,7(30),9,11(29),21,24(28),25-nonaen-20-one (3 entities in total) |
| Functional Keywords | syk kinase transferase inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35341.50 |
| Authors | Read, J.A.,Patel, J. (deposition date: 2022-11-01, release date: 2023-06-14, Last modification date: 2024-05-01) |
| Primary citation | Grimster, N.P.,Gingipalli, L.,Balazs, A.,Barlaam, B.,Boiko, S.,Boyd, S.,Dry, H.,Goldberg, F.W.,Ikeda, T.,Johnson, T.,Kawatkar, S.,Kemmitt, P.,Lamont, S.,Lorthioir, O.,Mfuh, A.,Patel, J.,Pike, A.,Read, J.,Romero, R.,Sarkar, U.,Sha, L.,Simpson, I.,Song, K.,Su, Q.,Wang, H.,Watson, D.,Wu, A.,Zehnder, T.E.,Zheng, X.,Li, S.,Dong, Z.,Yang, D.,Song, Y.,Wang, P.,Liu, X.,Dowling, J.E.,Edmondson, S.D. Optimization of a series of novel, potent and selective Macrocyclic SYK inhibitors. Bioorg.Med.Chem.Lett., 91:129352-129352, 2023 Cited by PubMed Abstract: Spleen tyrosine kinase (SYK) is a non-receptor cytoplasmic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signalling, inhibition of SYK has been a target of interest in a variety of diseases. Herein, we report the use of structure-based drug design to discover a series of potent macrocyclic inhibitors of SYK, with excellent kinome selectivity and in vitro metabolic stability. We were able to remove hERG inhibition through the optimization of physical properties, and utilized a pro-drug strategy to address permeability challenges. PubMed: 37270074DOI: 10.1016/j.bmcl.2023.129352 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.508 Å) |
Structure validation
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