Literature summary for 3.4.23.46 extracted from

Ghosh, A.K.; Venkateswara Rao, K.; Yadav, N.D.; Anderson, D.D.; Gavande, N.; Huang, X.; Terzyan, S.; Tang, J.
Structure-based design of highly selective beta-secretase inhibitors: synthesis, biological evaluation, and protein-ligand X-ray crystal structure (2012), J. Med. Chem., 55, 9195-9207.

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Cloned(Commentary)

Cloned (Comment)	Organism
-	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with inhibitor N-[(2S)-1-[[(3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide, to 2.2 A resolution. The amine functionality of the reduced amide isostere forms two tight hydrogen bonds with active site aspartic acid Asp228. The other active site Asp32 is not directly interacting with the reduced amide isostere. Asp32 is extensively hydrogen bonded the amide nitrogen of Gly34, the hydroxyl group of Ser35, and the amide nitrogen of Gly230. These interactions appear to lock Asp32 in a rigid conformation	Homo sapiens

Crystallization (Comment)

Organism

in complex with inhibitor N-[(2S)-1-[[(3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide, to 2.2 A resolution. The amine functionality of the reduced amide isostere forms two tight hydrogen bonds with active site aspartic acid Asp228. The other active site Asp32 is not directly interacting with the reduced amide isostere. Asp32 is extensively hydrogen bonded the amide nitrogen of Gly34, the hydroxyl group of Ser35, and the amide nitrogen of Gly230. These interactions appear to lock Asp32 in a rigid conformation

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
N-[(2S)-1-[[(2S,3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxohexan-2-yl]amino]-3-phenylpropan-2-yl]-7-ethyl-1-methyl-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indole-9-carboxamide 2,2-dioxide	compound designed specifically to interact with S1' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor exhibits exceedingly potent inhibitory activity and high selectivity over BACE 2 and cathepsin D	Homo sapiens
N-[(2S)-1-[[(3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide	compound designed specifically to interact with S1' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor exhibits exceedingly potent inhibitory activity and high selectivity over BACE 2 and cathepsin D	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P56817	-	-

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.0000004	-	N-[(2S)-1-[[(2S,3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxohexan-2-yl]amino]-3-phenylpropan-2-yl]-7-ethyl-1-methyl-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indole-9-carboxamide 2,2-dioxide	inhibitor exhibits a cellular IC50 value of 15 nM. pH not specified in the publication, temperature not specified in the publication	Homo sapiens
0.000025	-	N-[(2S)-1-[[(3S)-1-(butan-2-ylamino)-3-hydroxy-1-oxobutan-2-yl]amino]-3-phenylpropan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide	pH not specified in the publication, temperature not specified in the publication	Homo sapiens