Literature summary for 3.3.2.6 extracted from

Chen, Z.; Wu, Y.; Liu, Y.; Yang, S.; Chen, Y.; Lai, L.
Discovery of dual target inhibitors against cyclooxygenases and leukotriene A4 hydrolyase (2011), J. Med. Chem., 54, 3650-3660.

Crystallization (Commentary)

Crystallization (Comment)	Organism
molecular docking studies with inhibitors. Position and size of substituted groups plays a key role in the binding conformation of the compounds. Compounds without branches, and p-substituted compounds tend to bind LTA4H in the channel, forming a hydrogen bond between the pyrrolidine nitrogen atom and Gly269 main-chain oxygen atom. o- or m-Substituted compounds can stay at the entrance part of the pocket in a reversed orientation with three hydrogen bonds, the nitrogen atom to Gln136, the oxygen atom connected to alkyl group to His295, and the oxygen atom connected to bibenzyl to Gly268 main-chain nitrogen atom	Homo sapiens

Crystallization (Comment)

Organism

molecular docking studies with inhibitors. Position and size of substituted groups plays a key role in the binding conformation of the compounds. Compounds without branches, and p-substituted compounds tend to bind LTA4H in the channel, forming a hydrogen bond between the pyrrolidine nitrogen atom and Gly269 main-chain oxygen atom. o- or m-Substituted compounds can stay at the entrance part of the pocket in a reversed orientation with three hydrogen bonds, the nitrogen atom to Gln136, the oxygen atom connected to alkyl group to His295, and the oxygen atom connected to bibenzyl to Gly268 main-chain nitrogen atom

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
1-(2-(4-(2-(trifluoromethyl)phenoxy)phenoxy)ethyl)pyrrolidine	dual target inhibitor against cyclooxygenase COX-2 and leukotriene A4 hydrolyase in the enzyme assays and the human whole blood assay with IC50 values in the micromolar to submicromolar range. Inhibitor shows good selectivity for COX-2 over COX-1	Homo sapiens
1-(2-(4-(2-nitrophenoxy)phenoxy)ethyl)pyrrolidine	dual target inhibitor against cyclooxygenase COX-2 and leukotriene A4 hydrolyase in the enzyme assays and the human whole blood assay with IC50 values in the micromolar to submicromolar range. Inhibitor shows good selectivity for COX-2 over COX-1	Homo sapiens
1-(2-(4-(4-chlorophenoxy)phenoxy)ethyl)pyrrolidine	-	Homo sapiens
1-(2-(4-(4-fluorophenoxy)phenoxy)ethyl)pyrrolidine	-	Homo sapiens
1-(2-(4-(4-nitrophenoxy)phenoxy)ethyl)pyrrolidine	-	Homo sapiens
1-(2-(4-phenoxyphenoxy)ethyl)pyrrolidine	i.e. nimesulide	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.00003	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-phenoxyphenoxy)ethyl)pyrrolidine
0.00004	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-(4-chlorophenoxy)phenoxy)ethyl)pyrrolidine
0.00008	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-(4-fluorophenoxy)phenoxy)ethyl)pyrrolidine
0.00022	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-(2-(trifluoromethyl)phenoxy)phenoxy)ethyl)pyrrolidine
0.00037	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-(4-nitrophenoxy)phenoxy)ethyl)pyrrolidine
0.00068	-	pH 7.4, 37°C	Homo sapiens	1-(2-(4-(2-nitrophenoxy)phenoxy)ethyl)pyrrolidine