4DJY

Structure of BACE Bound to (R)-5-cyclopropyl-2-imino-3-methyl-5-(3-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)imidazolidin-4-one

Summary for 4DJY

• Entry DOI: 10.2210/pdb4djy/pdb
• Related: 4DJU 4DJV 4DJW 4DJX
• Descriptor: Beta-secretase 1, (2E,5R)-5-cyclopropyl-2-imino-3-methyl-5-{3-[5-(prop-1-yn-1-yl)pyridin-3-yl]phenyl}imidazolidin-4-one, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: bace1, alzheimers, 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: 2
• Total formula weight: 93488.85

Authors

Strickland, C.,Cumming, J. (deposition date: 2012-02-02, release date: 2012-03-21, Last modification date: 2012-04-04)

Primary citation

Cumming, J.N.,Smith, E.M.,Wang, L.,Misiaszek, J.,Durkin, J.,Pan, J.,Iserloh, U.,Wu, Y.,Zhu, Z.,Strickland, C.,Voigt, J.,Chen, X.,Kennedy, M.E.,Kuvelkar, R.,Hyde, L.A.,Cox, K.,Favreau, L.,Czarniecki, M.F.,Greenlee, W.J.,McKittrick, B.A.,Parker, E.M.,Stamford, A.W.
Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor.
Bioorg.Med.Chem.Lett., 22:2444-2449, 2012

PubMed Abstract: From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Aβ following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound.

PubMed: 22390835
DOI: 10.1016/j.bmcl.2012.02.013

Experimental method

X-RAY DIFFRACTION (1.86 Å)