2qmg
Structure of BACE Bound to SCH745966
Structural highlights
FunctionBACE1_HUMAN Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBased on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor.,Iserloh U, Pan J, Stamford AW, Kennedy ME, Zhang Q, Zhang L, Parker EM, McHugh NA, Favreau L, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):418-22. Epub 2007 Oct 18. PMID:17980584[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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