Structural highlights
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.[1] [2]
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
We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3.
Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.,Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
- ↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
- ↑ Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY. Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives. Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152 doi:10.1016/j.bmcl.2008.03.081
