2QU3

BACE1 with Compound 2

Summary for 2QU3

• Entry DOI: 10.2210/pdb2qu3/pdb
• Related: 2QU2
• Descriptor: Beta-secretase 1, N-[amino(imino)methyl]-2-[2-(2-chlorophenyl)-4-(4-propoxyphenyl)-3-thienyl]acetamide (3 entities in total)
• Functional Keywords: bace1, acylguanidine, inhibitor, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, protease, transmembrane, zymogen
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 46868.93

Authors

Chopra, R. (deposition date: 2007-08-03, release date: 2008-08-05, Last modification date: 2024-10-30)

Primary citation

Fobare, W.F.,Solvibile, W.R.,Robichaud, A.J.,Malamas, M.S.,Manas, E.,Turner, J.,Hu, Y.,Wagner, E.,Chopra, R.,Cowling, R.,Jin, G.,Bard, J.
Thiophene substituted acylguanidines as BACE1 inhibitors.
Bioorg.Med.Chem.Lett., 17:5353-5356, 2007

PubMed Abstract: A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay.

PubMed: 17761418
DOI: 10.1016/j.bmcl.2007.08.010

Experimental method

X-RAY DIFFRACTION (2 Å)