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4b1e

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Revision as of 16:45, 29 January 2020

New Aminoimidazoles as BACE-1 Inhibitors: From Rational Design to Ab- lowering in Brain

Structural highlights

4b1e is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1fkn, 1m4h, 1py1, 1sgz, 1tqf, 1ujj, 1ujk, 1w50, 1w51, 1xn2, 1xn3, 1xs7, 1ym2, 1ym4, 2b8l, 2b8v, 2fdp, 2va5, 2va6, 2va7, 2vie, 2vij, 2viy, 2viz, 2vj6, 2vj7, 2vj9, 2vkm, 2vnm, 2vnn, 2wez, 2wf0, 2wf1, 2wf2, 2wf3, 2wf4, 2wjo, 2xfi, 2xfj, 2xfk, 4acu, 4acx, 4azy, 4b00, 4b05, 4b0q, 4b1c, 4b1d
Activity:	Memapsin 2, with EC number 3.4.23.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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^[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
↑ 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. New Aminoimidazoles as beta-Secretase (BACE-1) Inhibitors Showing Amyloid-beta (Abeta) Lowering in Brain. J Med Chem. 2012 Oct 3. PMID:23017051 doi:http://dx.doi.org/10.1021/jm300991n

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b1e"

@@ Line 1: / Line 1: @@
 ==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]] 1.95&Aring;' scene=''>
+<StructureSection load='4b1e' size='340' side='right'caption='[[4b1e]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4b1e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B1E FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4b1e" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Memapsin 2]]
 [[Category: Berg, S von]]

4b1e

From Proteopedia

Revision as of 16:45, 29 January 2020

New Aminoimidazoles as BACE-1 Inhibitors: From Rational Design to Ab- lowering in Brain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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