2VNM

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-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)benzamide

Summary for 2VNM

• Entry DOI: 10.2210/pdb2vnm/pdb
• Related: 1FKN 1M4H 1PY1 1SGZ 1TQF 1UJJ 1UJK 1W50 1W51 1XN2 1XN3 1XS7 1YM2 1YM4 2B8L 2B8V 2VA5 2VA6 2VA7 2VIE 2VIJ 2VIY 2VIZ 2VJ6 2VJ7 2VJ9 2VKM 2VNN
• Descriptor: BETA-SECRETASE 1, N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-3-(1,1-dioxido-1,2-thiazinan-2-yl)-5-(ethylamino)benzamide (3 entities in total)
• Functional Keywords: hydrolase, alternative splicing, beta-site app cleaving enzyme, beta-secretase, aspartyl protease, asp-2, bace-1, zymogen, protease, membrane, memapsin-2, glycoprotein, transmembrane
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44998.73

Authors

Charrier, N.,Clarke, B.,Cutler, L.,Demont, E.,Dingwall, C.,Dunsdon, R.,East, P.,Hawkins, J.,Howes, C.,Hussain, I.,Jeffrey, P.,Maile, G.,Matico, R.,Mosley, J.,Naylor, A.,OBrien, A.,Redshaw, S.,Rowland, P.,Soleil, V.,Smith, K.J.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Wayne, G. (deposition date: 2008-02-05, release date: 2008-05-20, Last modification date: 2019-05-15)

Primary citation

Charrier, N.,Clarke, B.,Cutler, L.,Demont, E.,Dingwall, C.,Dunsdon, R.,East, P.,Hawkins, J.,Howes, C.,Hussain, I.,Jeffrey, P.,Maile, G.,Matico, R.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Rowland, P.,Soleil, V.,Smith, K.J.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Wayne, G.
Second Generation of Hydroxyethylamine Bace-1 Inhibitors: Optimizing Potency and Oral Bioavailability.
J.Med.Chem., 51:3313-, 2008

PubMed Abstract: BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.

PubMed: 18457381
DOI: 10.1021/JM800138H

Experimental method

X-RAY DIFFRACTION (1.79 Å)