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Literature summary for 1.3.5.2 extracted from

  • Davies, M.; Heikkila, T.; McConkey, G.; Fishwick, C.; Parsons, M.; Johnson, A.
    Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases (2009), J. Med. Chem., 52, 2683-2693.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
all compounds that were found to be inhibitors are predicted, using SPROUT, a software package for structure-based drug discovery and lead optimization, to bind in a manner similar to that observed for compound (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, with the planar headgroup making direct hydrogen bonds to residues Arg265, His185, and Tyr528. The biphenyl tail of each inhibitor is predicted to bind in the large hydrophobic region of the binding cavity, in a fashion analogous to that found for these inhibitors in human DHODH. The substituted biaryl moiety present in these inhibitors is predicted to occupy the binding cavity more extensively compared to that of compound (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide Plasmodium falciparum
in complex with inhibitors (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide, (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide, and (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Homo sapiens
(2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide inhibitor based on the active metabolite of the anti-inflammatory drug leflunomide. Comparison of inhibitory effect and binding to human and Plasmodium falciparum enzyme Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Homo sapiens Q02127
-
-
Plasmodium falciparum Q08210
-
-

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000022
-
-
Homo sapiens (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
0.00009
-
-
Homo sapiens (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.000117
-
-
Homo sapiens (2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
0.00013
-
-
Homo sapiens (2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.00013
-
-
Homo sapiens (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
0.00017
-
-
Homo sapiens (2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
0.00018
-
-
Homo sapiens (2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
0.00019
-
-
Homo sapiens (2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
0.0002
-
-
Homo sapiens (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.004
-
-
Plasmodium falciparum (2Z)-2-cyano-N-(2',3-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
0.0062
-
-
Plasmodium falciparum (2Z)-N-[2'-chloro-3-(trifluoromethyl)biphenyl-4-yl]-2-cyano-3-hydroxybut-2-enamide
0.0086
-
-
Plasmodium falciparum (2Z)-N-(3-chloro-2'-methoxybiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.0257
-
-
Plasmodium falciparum (2Z)-N-(biphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.0474
-
-
Plasmodium falciparum (2Z)-N-(2'-chlorobiphenyl-4-yl)-2-cyano-3-hydroxybut-2-enamide
0.0925
-
-
Plasmodium falciparum (2Z)-2-cyano-3-cyclopropyl-3-hydroxy-N-[4-(trifluoromethyl)phenyl]prop-2-enamide
0.165
-
-
Plasmodium falciparum (2Z)-2-cyano-N-(2,2'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide
0.182
-
-
Plasmodium falciparum (2Z)-2-cyano-N-(3'-ethoxybiphenyl-4-yl)-3-hydroxybut-2-enamide
0.2366
-
-
Plasmodium falciparum (2Z)-2-cyano-N-(2,3'-dichlorobiphenyl-4-yl)-3-hydroxybut-2-enamide