4pzw

Synthesis, Characterization and PK/PD Studies of a Series of Spirocyclic Pyranochromene BACE1 InhibitorsSynthesis, Characterization and PK/PD Studies of a Series of Spirocyclic Pyranochromene BACE1 Inhibitors

Structural highlights 4pzw is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BACE1_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. Publication Abstract from PubMed The development of 1,3,4,4a,5,10a-hexahydropyrano[3,4-b]chromene analogs as BACE1 inhibitors is described. Introduction of the spirocyclic pyranochromene scaffold yielded several advantages over previous generation cores, including increased potency, reduced efflux, and reduced CYP2D6 inhibition. Compound 13 (BACE1 IC50=110nM) demonstrated a reduction in CSF Abeta in wild type rats after a single dose. Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.,Volgraf M, Chan L, Huestis MP, Purkey HE, Burkard M, Geck Do M, Harris J, Hunt KW, Liu X, Lyssikatos JP, Rana S, Thomas AA, Vigers GP, Siu M Bioorg Med Chem Lett. 2014 Jun 1;24(11):2477-80. doi: 10.1016/j.bmcl.2014.04.012., Epub 2014 Apr 13. PMID:24780121 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase 3D structures

spinqualitylabelsall models 4pzw, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image