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Literature summary for 3.4.21.98 extracted from

  • Colarusso, S.; Koch, U.; Gerlach, B.; Steinkuhler, C.; De Francesco, R.; Altamura, S.; Matassa, V.G.; Narjes, F.
    Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling (2003), J. Med. Chem., 46, 345-348.
    View publication on PubMed
Search for more literature for 3.4.21.98

Protein Variants

Protein Variants Comment Organism
K136M Ki-values for the inhibitory amides 17,18 and 19 are about 2fold higher than that of the wild-type enzyme Hepacivirus C
K136R mutant is inhibited by the amides 17, 18 and 19 to nearly the same extent as the wild-type enzyme Hepacivirus C

Inhibitors

Inhibitors Comment Organism Structure
2-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid IC50: above 0.1 mM Hepacivirus C
2-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester IC50: 0.054 mM Hepacivirus C
3-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid IC50: 0.0092 mM Hepacivirus C
3-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester IC50: 0.025 mM Hepacivirus C
4-(2-[2-[2-(2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid highly specific Hepacivirus C
4-(2-[2-[2-(2-tert-Butoxycarbonylamino-4-carboxy-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid reversible competitive inhibitor, highly specific Hepacivirus C
4-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-3-chloro-benzoic acid IC50: 0.0007 mM Hepacivirus C
4-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-3-chloro-benzoic acid methyl ester IC50: 0.0032 mM Hepacivirus C
4-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid IC50: 0.002 mM Hepacivirus C
4-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester IC50: 0.017 mM Hepacivirus C
4-Benzyloxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid IC50: 0.04 mM Hepacivirus C
4-Isobutoxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid IC50: 0.019 mM Hepacivirus C
4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-2-mercapto-ethylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid IC50: 0.0065 mM Hepacivirus C
4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-3,3-difluoro-propenylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid
-
 Hepacivirus C
4-tert-Butoxycarbonylamino-4-[1-(1-carboxy-2-mercapto-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid IC50: above 0.2 mM Hepacivirus C
4-tert-Butoxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid IC50: 0.027 mM Hepacivirus C
4-[1-(1-Benzylcarbamoyl-2-mercapto-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-4-tert-butoxycarbonylamino-butyric acid IC50: above 0.2 mM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-2-mercapto-ethylcarbamoyl]-2-cyclohexyl-ethylcarbamoyl)-butyric acid IC50: 2 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[1-(1-benzylcarbamoyl-2-mercapto-ethylcarbamoyl)-2-cyclohexyl-ethylcarbamoyl]-butyric acid IC50: 250 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-ethylcarbamoyl]-butyric acid IC50: 7 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[1-(2-cyclohexyl-ethylcarbamoyl)-2-mercapto-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid IC50: 1540 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[1-(indan-2-ylcarbamoyl)-2-mercapto-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid IC50: 1700 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(2-phenyl-cyclopropylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid IC50: 1500 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(3-phenyl-propylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid IC50: 210 nM Hepacivirus C
4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(methyl-phenethyl-carbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid IC50: 0.07 mM Hepacivirus C
[1-[1-(2-Mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-propyl]-carbamic acid benzyl ester IC50: 0.4 mM Hepacivirus C

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
-
-

Synonyms

Synonyms Comment Organism
NS3/4A serine protease
-
 Hepacivirus C

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0006
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-4-carboxy-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid wild-type enzyme Hepacivirus C
0.0009
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-4-carboxy-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid mutant enzyme K136R Hepacivirus C
0.0013
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-4-carboxy-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid mutant enzyme K136M Hepacivirus C
0.0021
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid wild-type enzyme Hepacivirus C
0.0023
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid mutant enzyme K136R Hepacivirus C
0.004
-
 4-(2-[2-[2-(2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-4-methyl-pentanoylamino]-4,4-difluoro-but-2-enoylamino]-ethyl)-3-chloro-benzoic acid mutant enzyme K136M Hepacivirus C
0.0073
-
 4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-3,3-difluoro-propenylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid wild-type enzyme Hepacivirus C
0.0083
-
 4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-3,3-difluoro-propenylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid mutant enzyme K136R Hepacivirus C
0.0135
-
 4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-3,3-difluoro-propenylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid mutant enzyme K136M Hepacivirus C

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000002
-
 IC50: 2 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-2-mercapto-ethylcarbamoyl]-2-cyclohexyl-ethylcarbamoyl)-butyric acid
0.000007
-
 IC50: 7 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-ethylcarbamoyl]-butyric acid
0.00021
-
 IC50: 210 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(3-phenyl-propylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid
0.00025
-
 IC50: 250 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[1-(1-benzylcarbamoyl-2-mercapto-ethylcarbamoyl)-2-cyclohexyl-ethylcarbamoyl]-butyric acid
0.0007
-
 IC50: 0.0007 mM Hepacivirus C 4-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-3-chloro-benzoic acid
0.0015
-
 IC50: 1500 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(2-phenyl-cyclopropylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid
0.00154
-
 IC50: 1540 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[1-(2-cyclohexyl-ethylcarbamoyl)-2-mercapto-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid
0.0017
-
 IC50: 1700 nM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[1-(indan-2-ylcarbamoyl)-2-mercapto-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid
0.002
-
 IC50: 0.002 mM Hepacivirus C 4-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid
0.0032
-
 IC50: 0.0032 mM Hepacivirus C 4-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-3-chloro-benzoic acid methyl ester
0.0065
-
 IC50: 0.0065 mM Hepacivirus C 4-tert-Butoxycarbonylamino-4-(1-[1-[2-(2-chloro-phenyl)-ethylcarbamoyl]-2-mercapto-ethylcarbamoyl]-3-methyl-butylcarbamoyl)-butyric acid
0.0092
-
 IC50: 0.0092 mM Hepacivirus C 3-(2-[2-[2-(4-carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid
0.017
-
 IC50: 0.017 mM Hepacivirus C 4-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester
0.019
-
 IC50: 0.019 mM Hepacivirus C 4-Isobutoxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid
0.025
-
 IC50: 0.025 mM Hepacivirus C 3-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester
0.027
-
 IC50: 0.027 mM Hepacivirus C 4-tert-Butoxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid
0.04
-
 IC50: 0.04 mM Hepacivirus C 4-Benzyloxycarbonylamino-4-[1-(2-mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid
0.054
-
 IC50: 0.054 mM Hepacivirus C 2-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid methyl ester
0.07
-
 IC50: 0.07 mM Hepacivirus C 4-[2-[2-(2-Acetylamino-3-carboxy-propionylamino)-4-carboxy-butyrylamino]-3,3-diphenyl-propionylamino]-4-[2-cyclohexyl-1-[2-mercapto-1-(methyl-phenethyl-carbamoyl)-ethylcarbamoyl]-ethylcarbamoyl]-butyric acid
0.1
-
 IC50: above 0.1 mM Hepacivirus C 2-(2-[2-[2-(4-Carboxy-2-isobutoxycarbonylamino-butyrylamino)-4-methyl-pentanoylamino]-3-mercapto-propionylamino]-ethyl)-benzoic acid
0.2
-
 IC50: above 0.2 mM Hepacivirus C 4-[1-(1-Benzylcarbamoyl-2-mercapto-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-4-tert-butoxycarbonylamino-butyric acid
0.2
-
 IC50: above 0.2 mM Hepacivirus C 4-tert-Butoxycarbonylamino-4-[1-(1-carboxy-2-mercapto-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-butyric acid
0.4
-
 IC50: 0.4 mM Hepacivirus C [1-[1-(2-Mercapto-1-phenethylcarbamoyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-2-methyl-propyl]-carbamic acid benzyl ester