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