| Structural highlights
3k5c is a 3 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: | 3dv5, 3k5d, 3k5f, 3k5g |
| Gene: | BACE, BACE1, KIAA1149 (Homo sapiens) |
| 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
A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Abeta in human APP-wildtype transgenic (APP51/16) mice after oral administration.
Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application.,Lerchner A, Machauer R, Betschart C, Veenstra S, Rueeger H, McCarthy C, Tintelnot-Blomley M, Jaton AL, Rabe S, Desrayaud S, Enz A, Staufenbiel M, Paganetti P, Rondeau JM, Neumann U Bioorg Med Chem Lett. 2010 Jan 15;20(2):603-7. Epub 2009 Nov 22. PMID:19963375[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lerchner A, Machauer R, Betschart C, Veenstra S, Rueeger H, McCarthy C, Tintelnot-Blomley M, Jaton AL, Rabe S, Desrayaud S, Enz A, Staufenbiel M, Paganetti P, Rondeau JM, Neumann U. Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application. Bioorg Med Chem Lett. 2010 Jan 15;20(2):603-7. Epub 2009 Nov 22. PMID:19963375 doi:10.1016/j.bmcl.2009.11.092
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