4DCE
Crystal structure of human anaplastic lymphoma kinase in complex with a piperidine-carboxamide inhibitor
Summary for 4DCE
| Entry DOI | 10.2210/pdb4dce/pdb |
| Descriptor | ALK tyrosine kinase receptor, (3S)-N-(4-methylbenzyl)-1-{2-[(3,4,5-trimethoxyphenyl)amino]pyrimidin-4-yl}piperidine-3-carboxamide (3 entities in total) |
| Functional Keywords | receptor tyrosine kinase, inhibitor, npm-alk, eml4-alk, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell membrane ; Single-pass type I membrane protein : Q9UM73 |
| Total number of polymer chains | 2 |
| Total formula weight | 76119.43 |
| Authors | Whittington, D.A.,Epstein, L.F.,Chen, H. (deposition date: 2012-01-17, release date: 2012-02-08, Last modification date: 2024-04-03) |
| Primary citation | Bryan, M.C.,Whittington, D.A.,Doherty, E.M.,Falsey, J.R.,Cheng, A.C.,Emkey, R.,Brake, R.L.,Lewis, R.T. Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors. J.Med.Chem., 55:1698-1705, 2012 Cited by PubMed Abstract: Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC(50) = 0.174 μM) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R. PubMed: 22263917DOI: 10.1021/jm201565s PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.03 Å) |
Structure validation
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