4FRK
Crystal structure of BACE1 in complex with aminooxazoline xanthene 11a
Summary for 4FRK
| Entry DOI | 10.2210/pdb4frk/pdb |
| Related | 4FRI 4FRJ |
| Descriptor | Beta-secretase 1, IODIDE ION, (4S)-2'-(2-methylpropoxy)-7'-(pyrimidin-5-yl)spiro[1,3-oxazole-4,9'-xanthen]-2-amine, ... (5 entities in total) |
| Functional Keywords | membrane protein, alzheimer's disease, aspartic protease, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P56817 |
| Total number of polymer chains | 1 |
| Total formula weight | 46916.70 |
| Authors | Whittington, D.A.,Long, A.M. (deposition date: 2012-06-26, release date: 2012-09-12, Last modification date: 2012-12-12) |
| Primary citation | Huang, H.,La, D.S.,Cheng, A.C.,Whittington, D.A.,Patel, V.F.,Chen, K.,Dineen, T.A.,Epstein, O.,Graceffa, R.,Hickman, D.,Kiang, Y.H.,Louie, S.,Luo, Y.,Wahl, R.C.,Wen, P.H.,Wood, S.,Fremeau, R.T. Structure- and Property-Based Design of Aminooxazoline Xanthenes as Selective, Orally Efficacious, and CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer's Disease. J.Med.Chem., 55:9156-9169, 2012 Cited by PubMed Abstract: A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human β-secretase inhibitors. These compounds exhibited good isolated enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound 11a resulted in a significant reduction of CNS Aβ40 in naive rats. PubMed: 22928914DOI: 10.1021/jm300598e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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