2vij
HUMAN BACE-1 IN COMPLEX WITH 3-(1,1-DIOXIDOTETRAHYDRO-2H-1, 2-THIAZIN-2-YL)-5-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(1,2,3,4-TETRAHYDRO-1-NAPHTHALENYLAMINO) PROPYL)BENZAMIDE
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| , resolution 1.60Å | |||||||
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| Sites: | and | ||||||
| Ligands: | |||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Related: | 1M4H, 1SGZ, 1W50, 1W51, 1XS7, 1YM4, 1FKN, 1PY1, 1TQF, 1UJJ, 1UJK, 1XN2, 1XN3, 1YM2, 2B8L, 2B8V, 2VA5, 2VA6, 2VA7, 2VIE
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.
About this StructureAbout this Structure
2VIJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Skidmore J, Soleil V, Smith KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:18171615
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