Literature summary for 3.4.23.46 extracted from

Machauer, R.; Laumen, K.; Veenstra, S.; Rondeau, J.M.; Tintelnot-Blomley, M.; Betschart, C.; Jaton, A.L.; Desrayaud, S.; Staufenbiel, M.; Rabe, S.; Paganetti, P.; Neumann, U.
Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo (2009), Bioorg. Med. Chem. Lett., 19, 1366-1370.

Search for more literature for 3.4.23.46

Cloned(Commentary)

Cloned (Comment)	Organism
expression in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with inhibitor (3S,14R,16S)-16-[(1R)-1-hydroxy-2-([3-(1-methylethyl)benzyl]amino)ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione. The lipophilic isopropylbenzyl moiety of inhibitor is bound into the P2' subsite, lined on one side by the flap residues Val69, Pro70, Tyr71 and Thr72 and, on the other side, by Tyr198. In addition to hydrophobic contacts to Ser35, Val69, Tyr71 and Tyr198, this P' group is rather rigid, the position and orientation of the benzyl ring is not optimal for strong pi-stacking interactions with either Tyr71 or Tyr198	Homo sapiens

Crystallization (Comment)

Organism

in complex with inhibitor (3S,14R,16S)-16-[(1R)-1-hydroxy-2-([3-(1-methylethyl)benzyl]amino)ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione. The lipophilic isopropylbenzyl moiety of inhibitor is bound into the P2' subsite, lined on one side by the flap residues Val69, Pro70, Tyr71 and Thr72 and, on the other side, by Tyr198. In addition to hydrophobic contacts to Ser35, Val69, Tyr71 and Tyr198, this P' group is rather rigid, the position and orientation of the benzyl ring is not optimal for strong pi-stacking interactions with either Tyr71 or Tyr198

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(3S,14R,16S)-16-[(1R)-1-hydroxy-2-([3-(1-methylethyl)benzyl]amino)ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione	60fold preference for beta-secretase over cathepsin D	Homo sapiens
(3S,14R,16S)-16-[(1R)-1-hydroxy-2-([3-(1-methylethyl)benzyl]amino)ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione	inhibition of beta-secretase in the brain of amyloid precursor protein 51/16 transgenic mice after intravenous application	Mus musculus
(3S,14R,16S)-16-[(1S)-2-[[(1R)-3,3-dimethyl-7-(1-methylethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]-1-hydroxyethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione	inhibitory similarly to beta-sectretase and cathepsin D	Homo sapiens
(3S,14R,16S)-16-[(1S)-2-[[(1R)-3,3-dimethyl-7-(1-methylethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]-1-hydroxyethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione	inhibition of beta-secretase in the brain of amyloid precursor protein 51/16 transgenic mice after oral application	Mus musculus

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P56817	-	-
Mus musculus	-	-	-

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.000002	-	-	Homo sapiens	(3S,14R,16S)-16-[(1S)-2-[[(1R)-3,3-dimethyl-7-(1-methylethyl)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]-1-hydroxyethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione
0.000022	-	-	Homo sapiens	(3S,14R,16S)-16-[(1R)-1-hydroxy-2-([3-(1-methylethyl)benzyl]amino)ethyl]-3,4,14-trimethyl-1,4-diazacyclohexadecane-2,5-dione