| Structural highlights
2wf4 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.
| | Ligands: |
| | Related: | 1tqf, 1xn3, 1m4h, 2vnm, 2fdp, 1xn2, 2viy, 2va6, 2vie, 2vj6, 2viz, 2b8l, 1ym4, 2va5, 1sgz, 1ujk, 2b8v, 1fkn, 1xs7, 2vij, 2va7, 1ym2, 2vkm, 2vj9, 2vnn, 1py1, 1w50, 1ujj, 2vj7, 1w51, 2wf3, 2wf1, 2wf0, 2wez, 2wf2 |
| Activity: | Memapsin 2, with EC number 3.4.23.46 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
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 PubMed
Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration.
Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G Bioorg Med Chem Lett. 2009 Jul 1;19(13):3674-8. Epub 2009 Apr 5. PMID:19406640[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G. Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3674-8. Epub 2009 Apr 5. PMID:19406640 doi:10.1016/j.bmcl.2009.03.149
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