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Literature summary extracted from

  • Lorthiois, E.; Anderson, K.; Vulpetti, A.; Rogel, O.; Cumin, F.; Ostermann, N.; Steinbacher, S.; Mac Sweeney, A.; Delgado, O.; Liao, S.M.; Randl, S.; Ruedisser, S.; Dussauge, S.; Fettis, K.; Kieffer, L.; de Erkenez, A.; Yang, L.; Hartwieg, C.; Argikar, U.A.; La Bonte, L.R.; Newton, R.; Kansara, V.; Flohr, S.; Hommel, U.; Jaffee, B.; Maibaum, J.
    Discovery of highly potent and selective small-molecule reversible factor D inhibitors demonstrating alternative complement pathway inhibition in vivo (2017), J. Med. Chem., 60, 5717-5735 .
    View publication on PubMed

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.4.21.46 in complex with inhibitors, vapor diffusion method, using 22 or 27% (w/v) PEG3350, 50 mM NaCl and 100 mM HEPES/NaOH, pH 7.5 at 20°C Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(2-fluoro-3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(2-fluoro-3-trifluoromethylphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-chlorophenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-difluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-methoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(3-bromophenyl)amide] 2-[(1-carbamoyl-1H-indol-3-yl)amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(6-bromo-pyridin-2-yl)-amide] 2-[(1-carbamoyl-1H-indol-3-yl)-amide]
-
 Homo sapiens
3.4.21.46 (1R,3S,5R)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(6-trifluoromethyl-pyridin-2-yl)-amide]
-
 Homo sapiens
3.4.21.46 (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S)-N2-(diphenylmethyl)-N1-(1-methyl-1H-indol-3-yl)pyrrolidine-1,2-dicarboxamide
-
 Homo sapiens
3.4.21.46 (2S,4R)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S,4R)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S,4S)-4-amino-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S,4S)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S,4S)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (2S,4S)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide
-
 Homo sapiens
3.4.21.46 (R)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (S)-4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (S)-piperidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 (S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-methyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
-
 Homo sapiens
3.4.21.46 1-(2-((1R,3S,5R)-3-((6-bromopyridin-2-yl)carbamoyl)-2-azabicyclo[3.1.0]hexan-2-yl)-2-oxoethyl)-1H-indazole-3-carboxamide
-
 Homo sapiens
3.4.21.46 1-[2-[(1R,3S,5R)-3-[[(1R)-1-(3-chloro-2-fluorophenyl)ethyl]carbamoyl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-oxoethyl]-1H-indazole-3-carboxamide
-
 Homo sapiens
3.4.21.46 3-[[(2-carbamoyl-1H-indol-5-yl)oxy]methyl]benzoic acid
-
 Homo sapiens
3.4.21.46 methyl 2-([[(2S)-2-[[3-(trifluoromethoxy)phenyl]carbamoyl]pyrrolidine-1-carbonyl]amino]methyl)benzoate
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.4.21.46 complement factor B + H2O Homo sapiens
-
 fragment Ba + fragment Bb
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.46 Homo sapiens P00746
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.46 benzyloxycarbonyl-L-Lys-thiobenzyl ester + H2O
-
 Homo sapiens benzyloxycarbonyl-L-Lys + thiobenzoate
-
 ?
3.4.21.46 complement factor B + H2O
-
 Homo sapiens fragment Ba + fragment Bb
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.21.46 factor D
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.4.21.46 0.000006
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(6-bromo-pyridin-2-yl)-amide] 2-[(1-carbamoyl-1H-indol-3-yl)-amide]
3.4.21.46 0.000012
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(2-fluoro-3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.000014
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-azabicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(6-trifluoromethyl-pyridin-2-yl)-amide]
3.4.21.46 0.000023
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(2-fluoro-3-trifluoromethylphenyl)-amide]
3.4.21.46 0.000045
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(3-bromophenyl)amide] 2-[(1-carbamoyl-1H-indol-3-yl)amide]
3.4.21.46 0.00005
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.00005
-
 at pH 7.5 and 25°C Homo sapiens (2S,4R)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide]
3.4.21.46 0.00015
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-chlorophenyl)-amide]
3.4.21.46 0.00015
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-difluoromethoxyphenyl)-amide]
3.4.21.46 0.0003
-
 at pH 7.5 and 25°C Homo sapiens (2S,4S)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide
3.4.21.46 0.00032
-
 at pH 7.5 and 25°C Homo sapiens (1R,3S,5R)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-[(1-carbamoyl-1H-indol-3-yl)-amide] 3-[(3-methoxyphenyl)-amide]
3.4.21.46 0.00045
-
 at pH 7.5 and 25°C Homo sapiens (S)-4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.0005
-
 at pH 7.5 and 25°C Homo sapiens (2S,4S)-4-amino-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.0005
-
 at pH 7.5 and 25°C Homo sapiens (S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.00065
-
 at pH 7.5 and 25°C Homo sapiens (1S,2S,5R)-3-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 3-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.0007
-
 at pH 7.5 and 25°C Homo sapiens (2S,4S)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.00085
-
 at pH 7.5 and 25°C Homo sapiens (2S,4R)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.0014
-
 at pH 7.5 and 25°C Homo sapiens (2S,4S)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.0058
-
 at pH 7.5 and 25°C Homo sapiens (2S)-N2-(diphenylmethyl)-N1-(1-methyl-1H-indol-3-yl)pyrrolidine-1,2-dicarboxamide
3.4.21.46 0.014
-
 at pH 7.5 and 25°C Homo sapiens methyl 2-([[(2S)-2-[[3-(trifluoromethoxy)phenyl]carbamoyl]pyrrolidine-1-carbonyl]amino]methyl)benzoate
3.4.21.46 0.02
-
 at pH 7.5 and 25°C Homo sapiens (S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-methyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.022
-
 at pH 7.5 and 25°C Homo sapiens (S)-piperidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]
3.4.21.46 0.03
-
 at pH 7.5 and 25°C Homo sapiens (R)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]