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PDBsum entry 3k5c
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Hydrolase/hydrolase inhibitor
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PDB id
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3k5c
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References listed in PDB file
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Key reference
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Title
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Macrocyclic bace-1 inhibitors acutely reduce abeta in brain after po application.
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Authors
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A.Lerchner,
R.Machauer,
C.Betschart,
S.Veenstra,
H.Rueeger,
C.Mccarthy,
M.Tintelnot-Blomley,
A.L.Jaton,
S.Rabe,
S.Desrayaud,
A.Enz,
M.Staufenbiel,
P.Paganetti,
J.M.Rondeau,
U.Neumann.
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Ref.
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Bioorg Med Chem Lett, 2010,
20,
603-607.
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Macrocyclic peptidomimetic beta-Secretase (bace-1) inhibitors with activity in vivo
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Authors
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R.Machauer,
K.Laumen,
S.Veenstra,
J.-M.Rondeau,
M.Tintelnot-Blomley,
C.Betschart,
A.-L.Jaton,
S.Desrayaud,
M.Staufenbiel,
S.Rabe,
P.Paganetti,
U.Neumann.
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Ref.
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bioorg med chem lett, 2009,
19,
1366.
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