Literature summary for 3.4.22.27 extracted from

Tully, D.C.; Liu, H.; Alper, P.B.; Chatterjee, A.K.; Epple, R.; Roberts, M.J.; Williams, J.A.; Nguyen, K.T.; Woodmansee, D.H.; Tumanut, C.; Li, J.; Spraggon, G.; Chang, J.; Tuntland, T.; Harris, J.L.; Karanewsky, D.S.
Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: heterocyclic P3 (2006), Bioorg. Med. Chem. Lett., 16, 1975-1980.

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Crystallization (Commentary)

Crystallization (Comment)	Organism
crystallization of the enzyme in complex with an heterocyclic arylaminoethyl amide inhibitor, crystallization in presence of 0.2 M zinc acetate, X-ray diffraction structure determination and analysis at 1.8 A resolution	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(2R)-N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]tetrahydrofuran-2-carboxamide	IC50: 658 nM	Homo sapiens
(2R)-N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-2-carboxamide	IC50: 18 nM	Homo sapiens
(2S)-N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-2-carboxamide	IC50: 53 nM	Homo sapiens
(3R)-tetrahydrofuran-3-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate	IC50: 42 nM	Homo sapiens
(3S)-3-[(N-1,3-benzoxazol-2-yl-3-cyclohexyl-L-alanyl)amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoic acid	IC50: 12 nM	Homo sapiens
(3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoic acid	IC50: 27 nM	Homo sapiens
(3S)-tetrahydrofuran-3-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate	IC50: 49 nM	Homo sapiens
3-cyclohexyl-N2-(5-fluoro-1,3-benzoxazol-2-yl)-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 197 nM	Homo sapiens
3-cyclohexyl-N2-(6-fluoro-1,3-benzoxazol-2-yl)-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 43 nM	Homo sapiens
ethyl (3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoate	IC50: 71 nM	Homo sapiens
methyl 2-[[(1S)-1-(cyclohexylmethyl)-2-([2-[(4-fluorophenyl)amino]ethyl]amino)-2-oxoethyl]amino]-1,3-benzoxazole-6-carboxylate	IC50: 43 nM	Homo sapiens
additional information	synthesis and evaluation of heterocyclic arylaminoethyl amides as noncovalent inhibitors of cathepsin S, binding specificities of positions P1-P3 and of subsite S3, overview	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-1-benzofuran-2-carboxamide	IC50: 17 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-5-(3-fluorophenyl)furan-2-carboxamide	IC50: 34 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-5-[3-(trifluoromethyl)phenyl]furan-2-carboxamide	IC50: 11 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]furan-2-carboxamide	IC50: 47 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]furan-3-carboxamide	IC50: 6 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]tetrahydrofuran-3-carboxamide	IC50: 213 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]morpholine-4-carboxamide	IC50: 11 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydro-2H-pyran-4-carboxamide	IC50: 12 nM	Homo sapiens
N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-3-carboxamide	IC50: 21 nM	Homo sapiens
N2-(5-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 173 nM	Homo sapiens
N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[(1S)-1-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)methyl]-3-(methylsulfonyl)propyl]-L-alaninamide	IC50: 21 nM	Homo sapiens
N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[(1S)-2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 151 nM	Homo sapiens
N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 93 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-(1-methyl-2-[[3-(methylsulfonyl)phenyl]amino]ethyl)-L-alaninamide	IC50: 26 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-(1-methyl-2-[[4-(methylsulfonyl)phenyl]amino]ethyl)-L-alaninamide	IC50: 11 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2,2-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 15 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 15 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 12.3 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 3 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 19 nM	Homo sapiens
N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-methoxyphenyl)amino]-1-methylethyl]-L-alaninamide	IC50: 1 nM	Homo sapiens
N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[(1S)-2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide	IC50: 26 nM	Homo sapiens
N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)ethyl]-L-alaninamide	IC50: 222 nM	Homo sapiens
N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide	IC50: 94 nM	Homo sapiens
N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-[(4-methoxyphenyl)amino]ethyl]-L-alaninamide	IC50: 29 nM	Homo sapiens
N2-1,3-benzoxazol-2-yl-N-[(1R)-2-(benzyloxy)-1-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)methyl]ethyl]-3-cyclohexyl-L-alaninamide	IC50: 5 nM	Homo sapiens
tert-butyl (3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoate	IC50: 730 nM	Homo sapiens
tetrahydro-2H-pyran-4-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate	IC50: 12 nM	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
lysosome	-	Homo sapiens	5764	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Zn2+	bound at the active site, structure and ligand overview	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Synonyms

Synonyms	Comment	Organism
CatS	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000001	-	IC50: 1 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-methoxyphenyl)amino]-1-methylethyl]-L-alaninamide
0.000003	-	IC50: 3 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000005	-	IC50: 5 nM	Homo sapiens	N2-1,3-benzoxazol-2-yl-N-[(1R)-2-(benzyloxy)-1-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)methyl]ethyl]-3-cyclohexyl-L-alaninamide
0.000006	-	IC50: 6 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]furan-3-carboxamide
0.000011	-	IC50: 11 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-5-[3-(trifluoromethyl)phenyl]furan-2-carboxamide
0.000011	-	IC50: 11 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]morpholine-4-carboxamide
0.000011	-	IC50: 11 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-(1-methyl-2-[[4-(methylsulfonyl)phenyl]amino]ethyl)-L-alaninamide
0.000012	-	IC50: 12 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydro-2H-pyran-4-carboxamide
0.000012	-	IC50: 12 nM	Homo sapiens	tetrahydro-2H-pyran-4-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate
0.000012	-	IC50: 12 nM	Homo sapiens	(3S)-3-[(N-1,3-benzoxazol-2-yl-3-cyclohexyl-L-alanyl)amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoic acid
0.0000123	-	IC50: 12.3 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2-oxo-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000015	-	IC50: 15 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000015	-	IC50: 15 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-(5-fluoro-2,2-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000017	-	IC50: 17 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-1-benzofuran-2-carboxamide
0.000018	-	IC50: 18 nM	Homo sapiens	(2R)-N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-2-carboxamide
0.000019	-	IC50: 19 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000021	-	IC50: 21 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-3-carboxamide
0.000021	-	IC50: 21 nM	Homo sapiens	N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[(1S)-1-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)methyl]-3-(methylsulfonyl)propyl]-L-alaninamide
0.000026	-	IC50: 26 nM	Homo sapiens	N2-(7-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-(1-methyl-2-[[3-(methylsulfonyl)phenyl]amino]ethyl)-L-alaninamide
0.000026	-	IC50: 26 nM	Homo sapiens	N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[(1S)-2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000027	-	IC50: 27 nM	Homo sapiens	(3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoic acid
0.000029	-	IC50: 29 nM	Homo sapiens	N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-[(4-methoxyphenyl)amino]ethyl]-L-alaninamide
0.000034	-	IC50: 34 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]-5-(3-fluorophenyl)furan-2-carboxamide
0.000042	-	IC50: 42 nM	Homo sapiens	(3R)-tetrahydrofuran-3-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate
0.000043	-	IC50: 43 nM	Homo sapiens	3-cyclohexyl-N2-(6-fluoro-1,3-benzoxazol-2-yl)-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000043	-	IC50: 43 nM	Homo sapiens	methyl 2-[[(1S)-1-(cyclohexylmethyl)-2-([2-[(4-fluorophenyl)amino]ethyl]amino)-2-oxoethyl]amino]-1,3-benzoxazole-6-carboxylate
0.000047	-	IC50: 47 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]furan-2-carboxamide
0.000049	-	IC50: 49 nM	Homo sapiens	(3S)-tetrahydrofuran-3-yl [(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]carbamate
0.000053	-	IC50: 53 nM	Homo sapiens	(2S)-N-[(1S)-1-(cyclohexylmethyl)-2-[[(1S)-1-methyl-2-[[4-(trifluoromethoxy)phenyl]amino]ethyl]amino]-2-oxoethyl]tetrahydrofuran-2-carboxamide
0.000071	-	IC50: 71 nM	Homo sapiens	ethyl (3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoate
0.000093	-	IC50: 93 nM	Homo sapiens	N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000094	-	IC50: 94 nM	Homo sapiens	N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000151	-	IC50: 151 nM	Homo sapiens	N2-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[(1S)-2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)-1-methylethyl]-L-alaninamide
0.000173	-	IC50: 173 nM	Homo sapiens	N2-(5-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000197	-	IC50: 197 nM	Homo sapiens	3-cyclohexyl-N2-(5-fluoro-1,3-benzoxazol-2-yl)-N-[2-[(4-fluorophenyl)amino]ethyl]-L-alaninamide
0.000213	-	IC50: 213 nM	Homo sapiens	N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]tetrahydrofuran-3-carboxamide
0.000222	-	IC50: 222 nM	Homo sapiens	N2-1,3-benzoxazol-2-yl-3-cyclohexyl-N-[2-(5-fluoro-2,3-dihydro-1H-indol-1-yl)ethyl]-L-alaninamide
0.000658	-	IC50: 658 nM	Homo sapiens	(2R)-N-[(1S)-1-(cyclohexylmethyl)-2-oxo-2-[(2-[[4-(trifluoromethoxy)phenyl]amino]ethyl)amino]ethyl]tetrahydrofuran-2-carboxamide
0.00073	-	IC50: 730 nM	Homo sapiens	tert-butyl (3S)-3-[[N-(6-chloro-1,3-benzoxazol-2-yl)-3-cyclohexyl-L-alanyl]amino]-4-(5-fluoro-2,3-dihydro-1H-indol-1-yl)butanoate