Literature summary for 3.4.21.46 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 .

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Crystallization (Commentary)

Crystallization (Comment)	Organism
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

Inhibitors	Comment	Organism
(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
(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
(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
(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
(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
(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
(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
(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
(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
(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
(2S)-N2-(diphenylmethyl)-N1-(1-methyl-1H-indol-3-yl)pyrrolidine-1,2-dicarboxamide	-	Homo sapiens
(2S,4R)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide]	-	Homo sapiens
(2S,4R)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(2S,4S)-4-amino-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(2S,4S)-4-fluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(2S,4S)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(2S,4S)-4-methyl-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxy-phenyl)-amide	-	Homo sapiens
(R)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(S)-4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(S)-piperidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-carbamoyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
(S)-pyrrolidine-1,2-dicarboxylic acid 1-[(1-methyl-1H-indol-3-yl)-amide] 2-[(3-trifluoromethoxyphenyl)-amide]	-	Homo sapiens
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
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-[[(2-carbamoyl-1H-indol-5-yl)oxy]methyl]benzoic acid	-	Homo sapiens
methyl 2-([[(2S)-2-[[3-(trifluoromethoxy)phenyl]carbamoyl]pyrrolidine-1-carbonyl]amino]methyl)benzoate	-	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P00746	-	-

Substrates and Products (Substrate)

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

Synonyms

Synonyms	Comment	Organism
factor D	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
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]
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]
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]
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]
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]
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]
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]
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]
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]
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
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]
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]
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]
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]
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]
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]
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]
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]
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
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
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]
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]
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]