HUMAN BACE-1 IN COMPLEX WITH 6-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-3-(((3-(METHYLOXY)PHENYL)METHYL)AMINO)-1-(PHENYLMETHYL)PROPYL)-1-METHYL-1,3,4,5-TETRAHYDRO-2,1-BENZOTHIAZEPINE-8-CARBOXAMIDE 2,2-DIOXIDE
2wf3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer's disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors.
Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent.,Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Hawkins J, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G Bioorg Med Chem Lett. 2009 Jul 1;19(13):3669-73. Epub 2009 Apr 5. PMID:19477642[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Hawkins J, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G. Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3669-73. Epub 2009 Apr 5. PMID:19477642 doi:10.1016/j.bmcl.2009.03.150
