3N4L

BACE-1 in complex with ELN380842

Summary for 3N4L

• Entry DOI: 10.2210/pdb3n4l/pdb
• Descriptor: Beta-secretase 1, N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(1H-pyrazol-1-yl)phenyl]cyclohexyl}amino)propyl]acetamide (3 entities in total)
• Functional Keywords: bace, hydroxyethylamine, beta secretase, alzheimer's disease, ad, beta-amyloid precursor protein, beta-app, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 137783.06

Authors

Yao, N.H. (deposition date: 2010-05-21, release date: 2010-11-24, Last modification date: 2024-10-30)

Primary citation

Truong, A.P.,Probst, G.D.,Aquino, J.,Fang, L.,Brogley, L.,Sealy, J.M.,Hom, R.K.,Tucker, J.A.,John, V.,Tung, J.S.,Pleiss, M.A.,Konradi, A.W.,Sham, H.L.,Dappen, M.S.,Toth, G.,Yao, N.,Brecht, E.,Pan, H.,Artis, D.R.,Ruslim, L.,Bova, M.P.,Sinha, S.,Yednock, T.A.,Zmolek, W.,Quinn, K.P.,Sauer, J.M.
Improving the permeability of the hydroxyethylamine BACE-1 inhibitors: structure-activity relationship of P2' substituents.
Bioorg.Med.Chem.Lett., 20:4789-4794, 2010

PubMed Abstract: Herein we describe further evolution of hydroxyethylamine inhibitors of BACE-1 with enhanced permeability characteristics necessary for CNS penetration. Variation at the P2' position of the inhibitor with more polar substituents led to compounds 19 and 32, which retained the potency of more lipophilic analog 1 but with much higher observed passive permeability in MDCK cellular assay.

PubMed: 20634069
DOI: 10.1016/j.bmcl.2010.06.112

Experimental method

X-RAY DIFFRACTION (2.7 Å)