2VIJ

Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- 2-yl)-5-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(1,2,3,4- tetrahydro-1-naphthalenylamino)propyl)benzamide

Summary for 2VIJ

• Entry DOI: 10.2210/pdb2vij/pdb
• Related: 1FKN 1M4H 1PY1 1SGZ 1TQF 1UJJ 1UJK 1W50 1W51 1XN2 1XN3 1XS7 1YM2 1YM4 2B8L 2B8V 2VA5 2VA6 2VA7 2VIE
• Descriptor: BETA-SECRETASE 1, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]propyl}-3-(1,1-dioxido-1,2-thiazinan-2-yl)-5-(ethylamino)benzamide (3 entities in total)
• Functional Keywords: alternative splicing, beta-site app cleaving enzyme, beta-secretase, aspartyl protease, asp-2, bace-1, zymogen, protease, membrane, hydrolase, memapsin-2, glycoprotein, transmembrane
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44942.86

Authors

Beswick, P.,Charrier, N.,Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Gleave, R.,Hawkins, J.,Hussain, I.,Johnson, C.N.,Macpherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Skidmore, J.,Soleil, V.,Smith, K.J.,Stanway, S.,Stemp, G.,Stuart, A.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G. (deposition date: 2007-12-04, release date: 2008-01-29, Last modification date: 2024-11-13)

Primary citation

Beswick, P.,Charrier, N.,Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Gleave, R.,Hawkins, J.,Hussain, I.,Johnson, C.N.,Macpherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Skidmore, J.,Soleil, V.,Smith, K.J.,Stanway, S.,Stemp, G.,Stuart, A.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G.
Bace-1 Inhibitors Part 3: Identification of Hydroxy Ethylamines (Heas) with Nanomolar Potency in Cells.
Bioorg.Med.Chem.Lett., 18:1022-, 2008

PubMed Abstract: This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

PubMed: 18171615
DOI: 10.1016/J.BMCL.2007.12.020

Experimental method

X-RAY DIFFRACTION (1.6 Å)