4b1e
From Proteopedia
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| - | [[Image:4b1e.jpg|left|200px]] | ||
| - | + | ==New Aminoimidazoles as BACE-1 Inhibitors: From Rational Design to Ab- lowering in Brain== | |
| + | <StructureSection load='4b1e' size='340' side='right'caption='[[4b1e]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4b1e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B1E FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6T6:(2R)-2-METHYL-5-PHENYL-2-(3-PYRIDIN-3-YLPHENYL)-2,3-DIHYDRO-1H-IMIDAZOL-4-AMINE'>6T6</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4b1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b1e OCA], [https://pdbe.org/4b1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b1e RCSB], [https://www.ebi.ac.uk/pdbsum/4b1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b1e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Amino-2H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer's disease. Synthetic methods, crystal structures, and structure-activity relationships for target activity, permeability, and hERG activity are reported and discussed. Compound (S)-1m was one of the most promising compounds in this report, with high potency in the cellular assay and a good overall profile. When guinea pigs were treated with compound (S)-1m, a concentration and time dependent decrease in Abeta40 and Abeta42 levels in plasma, brain, and CSF was observed. The maximum reduction of brain Abeta was 40-50%, 1.5 h after oral dosing (100 mumol/kg). The results presented highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low effect on hERG, in combination with a fair CNS exposure in vivo. | ||
| - | + | New Aminoimidazoles as beta-Secretase (BACE-1) Inhibitors Showing Amyloid-beta (Abeta) Lowering in Brain.,Gravenfors Y, Viklund J, Blid J, Ginman T, Karlstrom S, Kihlstrom J, Kolmodin K, Lindstrom J, von Berg S, von Kieseritzky F, Slivo C, Swahn BM, Olsson LL, Johansson P, Eketjall S, Falting J, Jeppsson F, Stromberg K, Janson J, Rahm F J Med Chem. 2012 Oct 3. PMID:23017051<ref>PMID:23017051</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4b1e" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | [[ | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: Blid | + | __TOC__ |
| - | [[Category: Eketjall | + | </StructureSection> |
| - | [[Category: Falting | + | [[Category: Homo sapiens]] |
| - | [[Category: Ginman | + | [[Category: Large Structures]] |
| - | [[Category: Gravenfors | + | [[Category: Blid J]] |
| - | [[Category: Janson | + | [[Category: Eketjall S]] |
| - | [[Category: Jeppsson | + | [[Category: Falting J]] |
| - | [[Category: Johansson | + | [[Category: Ginman T]] |
| - | [[Category: Karlstrom | + | [[Category: Gravenfors Y]] |
| - | + | [[Category: Janson J]] | |
| - | [[Category: Kihlstrom | + | [[Category: Jeppsson F]] |
| - | [[Category: Kolmodin | + | [[Category: Johansson P]] |
| - | [[Category: Lindstrom | + | [[Category: Karlstrom S]] |
| - | [[Category: Olsson | + | [[Category: Kihlstrom J]] |
| - | [[Category: Rahm | + | [[Category: Kolmodin K]] |
| - | [[Category: Slivo | + | [[Category: Lindstrom J]] |
| - | [[Category: Stromberg | + | [[Category: Olsson L]] |
| - | [[Category: Swahn | + | [[Category: Rahm F]] |
| - | [[Category: Viklund | + | [[Category: Slivo C]] |
| - | [[Category: | + | [[Category: Stromberg K]] |
| - | [[Category: | + | [[Category: Swahn B]] |
| + | [[Category: Viklund J]] | ||
| + | [[Category: Von Berg S]] | ||
| + | [[Category: Von Kieseritzky F]] | ||
Current revision
New Aminoimidazoles as BACE-1 Inhibitors: From Rational Design to Ab- lowering in Brain
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Categories: Homo sapiens | Large Structures | Blid J | Eketjall S | Falting J | Ginman T | Gravenfors Y | Janson J | Jeppsson F | Johansson P | Karlstrom S | Kihlstrom J | Kolmodin K | Lindstrom J | Olsson L | Rahm F | Slivo C | Stromberg K | Swahn B | Viklund J | Von Berg S | Von Kieseritzky F
