6PDJ
Tyrosine-protein kinase LCK bound to Compound 11
Summary for 6PDJ
| Entry DOI | 10.2210/pdb6pdj/pdb |
| Descriptor | Tyrosine-protein kinase Lck, N-{4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]-3-methylphenyl}-1-methyl-1H-indazole-3-carboxamide, 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID, ... (6 entities in total) |
| Functional Keywords | inhibitor, signaling protein, signaling protein-inhibitor complex, signaling protein/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34318.61 |
| Authors | Critton, D.A. (deposition date: 2019-06-19, release date: 2019-10-09, Last modification date: 2024-10-30) |
| Primary citation | O'Malley, D.P.,Ahuja, V.,Fink, B.,Cao, C.,Wang, C.,Swanson, J.,Wee, S.,Gavai, A.V.,Tokarski, J.,Critton, D.,Paiva, A.A.,Johnson, B.M.,Szapiel, N.,Xie, D. Discovery of Pyridazinone and Pyrazolo[1,5-a]pyridine Inhibitors of C-Terminal Src Kinase. Acs Med.Chem.Lett., 10:1486-1491, 2019 Cited by PubMed Abstract: C-terminal Src kinase (CSK) functions as a negative regulator of T cell activation through inhibitory phosphorylation of LCK, so inhibitors of CSK are of interest as potential immuno-oncology agents. Screening of an internal kinase inhibitor collection identified pyridazinone lead , and a series of modifications led to optimized compound . Compound showed potent activity in biochemical and cellular assays and demonstrated the ability to increase T cell proliferation induced by T cell receptor signaling. Compound gave extended exposure in mice upon oral dosing and produced a functional response (decrease in LCK phosphorylation) in mouse spleens at 6 h post dose. PubMed: 31620238DOI: 10.1021/acsmedchemlett.9b00354 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.81 Å) |
Structure validation
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