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Literature summary for 3.4.21.98 extracted from

  • Lin, T.I.; Lenz, O.; Fanning, G.; Verbinnen, T.; Delouvroy, F.; Scholliers, A.; Vermeiren, K.; Rosenquist, A.; Edlund, M.; Samuelsson, B.; Vrang, L.; de Kock, H.; Wigerinck, P.; Raboisson, P.; Simmen, K.
    In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor (2009), Antimicrob. Agents Chemother., 53, 1377-1385.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.21.98

Application

Application Comment Organism
medicine inhibitor shows selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and a favorable pharmacokinetic profile Hepacivirus C
medicine inhibitor shows selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and a favorable pharmacokinetic profile hepatitis C virus genotype 1a

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Hepacivirus C
expressed in Escherichia coli hepatitis C virus genotype 1a

Inhibitors

Inhibitors Comment Organism Structure
N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide HCV replication in a cellular assay (subgenomic 1b replicon) is inhibited with a half-maximal effective concentration (EC50) of 8 nM. The compound is synergistic with alpha interferon and an NS5B inhibitor in the replicon model and additive with ribavirin. In rats, the compound is extensively distributed to the liver and intestinal tract, and the absolute bioavailability is 44% after a single oral administration. Compound concentrations detected in both plasma and liver at 8 h postdosing are above the EC99 value measured in the replicon Hepacivirus C
N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide HCV replication in a cellular assay (subgenomic 1b replicon) is inhibited with a half-maximal effective concentration (EC50) of 8 nM. The compound is synergistic with alpha interferon and an NS5B inhibitor in the replicon model and additive with ribavirin. In rats, the compound is extensively distributed to the liver and intestinal tract, and the absolute bioavailability is 44% after a single oral administration. Compound concentrations detected in both plasma and liver at 8 h postdosing are above the EC99 value measured in the replicon hepatitis C virus genotype 1a

Organism

Organism UniProt Comment Textmining
Hepacivirus C
-
 genotypes 1b
-
hepatitis C virus genotype 1a
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
RetS1 peptide substrate + H2O
-
 Hepacivirus C ?
-
 ?
RetS1 peptide substrate + H2O
-
 hepatitis C virus genotype 1a ?
-
 ?

Synonyms

Synonyms Comment Organism
NS3 serine proteinase
-
 Hepacivirus C
NS3 serine proteinase
-
 hepatitis C virus genotype 1a

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0000004
-
 N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide
-
 Hepacivirus C
0.0000005
-
 N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide
-
 hepatitis C virus genotype 1a