| Hepatitis C virus |
EC90 |
= |
0.52 |
uM |
Antiviral activity against HCV infected in human clone A cells |
CHEMBL1255219 |
| Hepatitis C virus |
Inhibition |
= |
25.9 |
% |
Antiviral activity against HCV infected in human clone A cells assessed as inhibition of cellular rRNA replication at 50 uM |
CHEMBL1255219 |
| No relevant target |
T1/2 |
= |
22.0 |
hr |
Half life in simulated gastric fluid at pH 1.2 at 50 ug/mL |
CHEMBL1255219 |
| No relevant target |
T1/2 |
> |
24.0 |
hr |
Half life in simulated intestinal fluid of pH 7.5 at 50 ug/mL |
CHEMBL1255219 |
| Plasma |
T1/2 |
> |
24.0 |
hr |
Half life in human plasma at 100 uM |
CHEMBL1255219 |
| ADMET |
T1/2 |
= |
0.57 |
hr |
Half life in human liver S9 fraction at 100 uM |
CHEMBL1255219 |
| Rattus norvegicus |
Cmax |
= |
1934.0 |
ng/g |
Cmax in rat liver assessed as 2'-F-2'-C-Methyluridine-5''-TP level at 50 mg/kg, po |
CHEMBL1255219 |
| Rattus norvegicus |
Tmax |
= |
4.0 |
hr |
Tmax in rat liver assessed as 2'-F-2'-C-Methyluridine-5''-TP level at 50 mg/kg, po |
CHEMBL1255219 |
| Rattus norvegicus |
AUC |
= |
16796.0 |
ng.hr/g |
AUC (0 to t) in rat liver assessed as 2'-F-2'-C-Methyluridine-5''-TP level at 50 mg/kg, po |
CHEMBL1255219 |
| Rattus norvegicus |
AUC |
= |
18080.0 |
ng.hr/g |
AUC (0 to infinity) in rat liver assessed as 2'-F-2'-C-Methyluridine-5''-TP level at 50 mg/kg, po |
CHEMBL1255219 |
| Canis familiaris |
Cmax |
= |
11670.38 |
nM |
Cmax in dog plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Canis familiaris |
Tmax |
= |
0.5 |
hr |
Tmax in dog plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Canis familiaris |
AUC |
= |
6903.0 |
ng.hr.mL-1 |
AUC (0 to infinity) in dog plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Canis familiaris |
AUC |
= |
6894.0 |
ng.hr.mL-1 |
AUC (0 to t) in dog plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Canis familiaris |
Drug uptake |
= |
612.0 |
ng/g |
Metabolic stability in dog liver assessed as prodrug level at 50 mg/kg, po |
CHEMBL1255219 |
| Canis familiaris |
Drug uptake |
= |
10560.0 |
ng/g |
Metabolic stability in dog liver assessed as 2'-F-2'-C-Methyluridine-5''-triphosphate level at 50 mg/kg, po |
CHEMBL1255219 |
| Cynomolgus monkey |
Cmax |
= |
62.33 |
nM |
Cmax in cynomolgus monkey plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Cynomolgus monkey |
Tmax |
= |
1.0 |
hr |
Tmax in cynomolgus monkey plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Cynomolgus monkey |
AUC |
= |
170.0 |
ng.hr.mL-1 |
AUC (0 to infinity) in cynomolgus monkey plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Cynomolgus monkey |
AUC |
= |
86.0 |
ng.hr.mL-1 |
AUC (0 to t) in cynomolgus monkey plasma at 50 mg/kg, po qd for 4 days |
CHEMBL1255219 |
| Cynomolgus monkey |
Drug uptake |
= |
177.0 |
ng/g |
Metabolic stability in cynomolgus monkey liver assessed as prodrug level at 50 mg/kg, po |
CHEMBL1255219 |
| Cynomolgus monkey |
Drug uptake |
= |
57.0 |
ng/g |
Metabolic stability in cynomolgus monkey liver assessed as 2'-F-2'-C-Methyluridine-5''-triphosphate level at 50 mg/kg, po |
CHEMBL1255219 |
| ADMET |
permeability |
= |
0.46 |
nm/s |
Permeability by PAMPA assay |
CHEMBL1255219 |
| ADMET |
Activity |
|
|
|
Cytotoxicity against HuH7 cells at 100 uM |
CHEMBL1255219 |
| HepG2 |
Activity |
|
|
|
Cytotoxicity against human HepG2 cells at 100 uM |
CHEMBL1255219 |
| ADMET |
Activity |
|
|
|
Cytotoxicity against human BxPC3 cells at 100 uM |
CHEMBL1255219 |
| CCRF-CEM |
Activity |
|
|
|
Cytotoxicity against human CEM cells at 100 uM |
CHEMBL1255219 |
| ADMET |
IC50 |
> |
50000.0 |
nM |
Cytotoxicity against human erythroid progenitor cells after 14 to 16 hrs |
CHEMBL1255219 |
| ADMET |
IC50 |
> |
50000.0 |
nM |
Cytotoxicity against human myeloid progenitor cells after 14 to 16 hrs |
CHEMBL1255219 |
| Rattus norvegicus |
Activity |
|
|
|
Toxicity in rat assessed as mortality at 50 to 1800 mg/kg, po after 14 days |
CHEMBL1255219 |
| Rattus norvegicus |
Activity |
|
|
|
Toxicity in rat assessed as change in body weight at 50 to 1800 mg/kg, po after 14 days |
CHEMBL1255219 |
| Rattus norvegicus |
Activity |
|
|
|
Toxicity in rat assessed as change in macroscopic pathology at 50 to 1800 mg/kg, po after 14 days |
CHEMBL1255219 |
| Rattus norvegicus |
Activity |
|
|
|
Toxicity in rat assessed as change in liver weight at 50 to 1800 mg/kg, po after 14 days |
CHEMBL1255219 |
| Rattus norvegicus |
Activity |
|
|
|
Toxicity in rat assessed as change in kidney weight at 50 to 1800 mg/kg, po after 14 days |
CHEMBL1255219 |
| Hepatitis C virus |
EC90 |
= |
0.39 |
uM |
Antiviral activity against Hepatitis C virus harboring NS5B polymerase S96T/N142T mutant gene infected in human lunet cells by luciferase-based replicon assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.45 |
uM |
Antiviral activity against Hepatitis C virus harboring wild-type NS5B infected in human HuH7 cells by luciferase-based replicon assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
7.4 |
uM |
Antiviral activity against Hepatitis C virus harboring NS5B polymerase S282T mutant gene infected in human HuH7 cells by luciferase-based replicon assay |
CHEMBL1629705 |
| Hepatitis C virus |
Selectivity ratio |
= |
16.4 |
|
Selectivity ratio of EC90 for Hepatitis C virus harboring NS5B polymerase S282T mutant gene to EC90 for Hepatitis C virus harboring wild-type NS5B polymerase |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.52 |
uM |
Antiviral activity against Hepatitis C virus harboring wild-type NS5B infected in human lunet cells by luciferase-based replicon assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.39 |
uM |
Antiviral activity against Hepatitis C virus harboring NS5B polymerase S96T mutant gene infected in human lunet cells by luciferase-based replicon assay |
CHEMBL1629705 |
| Hepatitis C virus |
Selectivity ratio |
= |
0.66 |
|
Selectivity ratio of EC90 for Hepatitis C virus harboring NS5B polymerase S96T mutant gene to EC90 for HCV harboring wild type NS5B polymerase |
CHEMBL1629705 |
| Hepatitis C virus |
FC |
= |
0.58 |
|
Antiviral activity against Hepatitis C virus assessed as log reduction in viral RNA at 0.1 uM after 3 weeks |
CHEMBL1629705 |
| Hepatitis C virus |
FC |
= |
4.0 |
|
Antiviral activity against Hepatitis C virus assessed as log reduction in viral RNA at 1 uM after 3 weeks |
CHEMBL1629705 |
| Hepatitis C virus |
FC |
> |
5.0 |
|
Antiviral activity against Hepatitis C virus assessed as log reduction in viral RNA at 2 uM after 3 weeks |
CHEMBL1629705 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against Hepatitis C virus assessed as inhibition of viral rebound at 1 uM after 3 weeks in presence of G418 |
CHEMBL1629705 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against Hepatitis C virus assessed as inhibition of viral rebound at 2 uM after 3 weeks in presence of G418 |
CHEMBL1629705 |
| Hepatitis C virus |
Activity |
|
|
|
Antiviral activity against Hepatitis C virus assessed as clearance of HCV from replicon cells at 1 uM |
CHEMBL1629705 |
| Hepatitis C virus |
Activity |
|
|
|
Antiviral activity against Hepatitis C virus assessed as clearance of HCV from replicon cells at 2 uM |
CHEMBL1629705 |
| DNA-directed RNA polymerase II subunit RPB1 |
FC |
= |
5.0 |
|
Inhibition of human RNA polymerase at 2 uM |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
1340.0 |
nM |
Antiviral activity against Hepatitis C virus Con1 infected in human lunet cells assessed as inhibition of viral RNA replication after 4 days by luciferase reporter gene assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
4.32 |
uM |
Antiviral activity against Hepatitis C virus isolate Con1 infected in human HuH-7 cells assessed as inhibition of viral RNA replication after 4 days by luciferase reporter gene assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
90.0 |
nM |
Antiviral activity against Hepatitis C virus isolate Con1 harboring Btat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
93.0 |
nM |
Antiviral activity against Hepatitis C virus genotype 1b harboring Ntat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
430.0 |
nM |
Antiviral activity against Hepatitis C virus H77 harboring Htat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
180.0 |
nM |
Antiviral activity against Hepatitis C virus JFH1 assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
190.0 |
nM |
Antiviral activity against Hepatitis C virus H77 |
CHEMBL1629705 |
| West Nile virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against West Nile virus New York by neutral red assay |
CHEMBL1629705 |
| NON-PROTEIN TARGET |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against Yellow fever virus 17D by neutral red assay |
CHEMBL1629705 |
| Influenza A virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against Influenza A virus (A/Brisbane/59/2007 (H1N1)) infected in HFF by neutral red assay |
CHEMBL1629705 |
| Influenza A virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against Influenza A virus (A/Viet Nam/1203/2004(H5N1)) infected in HFF by neutral red assay |
CHEMBL1629705 |
| Influenza A virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against Influenza A virus (A/Brisbane/10/2007(H3N2)) infected in HFF by neutral red assay |
CHEMBL1629705 |
| Hepatitis B virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against Hepatitis B virus infected in human HepAD38 cells by quantitative real-time PCR |
CHEMBL1629705 |
| Human immunodeficiency virus |
EC50 |
> |
100000.0 |
nM |
Antiviral activity against HIV infected in human HeLaP4 cells by beta-galactosidase-based reporter gene assay |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human HuH7 cells assessed as effect on cellular GAPDH RNA level after 8 days by quantitative real-time PCR |
CHEMBL1629705 |
| HepG2 |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human HepG2 cells assessed as effect on cellular GAPDH RNA level after 8 days by quantitative real-time PCR |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human BxPC3 cells assessed as effect on cellular GAPDH RNA level after 8 days by quantitative real-time PCR |
CHEMBL1629705 |
| CCRF-CEM |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human CEM cells assessed as effect on cellular GAPDH RNA level after 8 days by quantitative real-time PCR |
CHEMBL1629705 |
| HFF |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against HFF |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human HepAD38 cells |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human HeLaP4 cells |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
3.81 |
uM |
Antiviral activity against Hepatitis C virus Con1 infected in human lunet cells assessed as inhibition of viral RNA replication after 4 days by luciferase reporter gene assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.65 |
uM |
Antiviral activity against Hepatitis C virus isolate Con1 harboring Btat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.75 |
uM |
Antiviral activity against Hepatitis C virus genotype 1b harboring Ntat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
1.22 |
uM |
Antiviral activity against Hepatitis C virus H77 harboring Htat protein assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.52 |
uM |
Antiviral activity against Hepatitis C virus JFH1 assessed as viral RNA level by quantitative real-time PCR |
CHEMBL1629705 |
| Hepatitis C virus |
EC90 |
= |
0.34 |
uM |
Antiviral activity against Hepatitis C virus H77 |
CHEMBL1629705 |
| HFF |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against HFF |
CHEMBL1629705 |
| HFF |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against HFF |
CHEMBL1629705 |
| HFF |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against HFF |
CHEMBL1629705 |
| HFF |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against HFF |
CHEMBL1629705 |
| HepG2 |
Activity |
|
|
|
Mitochondrial toxicity in human HepG2 cells assessed as effect on mitochondrial cytochrome c oxidase subunit 2 gene level up to 100 uM after 14 days by real-time PCR assay |
CHEMBL1629705 |
| CCRF-CEM |
Activity |
|
|
|
Mitochondrial toxicity in human CEM cells assessed as effect on mitochondrial cytochrome c oxidase subunit 2 gene level up to 100 uM after 14 days by quantitative real-time PCR assay |
CHEMBL1629705 |
| HepG2 |
Activity |
|
|
|
Cytotoxicity against human HepG2 cells assessed as effect on ribosome RNA gene level at up to 100 uM after 14 days by quantitative real-time PCR assay |
CHEMBL1629705 |
| CCRF-CEM |
Activity |
|
|
|
Cytotoxicity against human CEM cells assessed as effect on ribosome RNA gene level at up to 100 uM after 14 days by quantitative real-time PCR assay |
CHEMBL1629705 |
| HepG2 |
CC90 |
= |
12.77 |
uM |
Cytotoxicity against human HepG2 cells |
CHEMBL1629705 |
| CCRF-CEM |
CC90 |
= |
28.5 |
uM |
Cytotoxicity against human CEM cells |
CHEMBL1629705 |
| HepG2 |
CC90 |
< |
3.0 |
uM |
Cytotoxicity against human HepG2 cells assessed as inhibition of mitochondrial DNA synthesis |
CHEMBL1629705 |
| CCRF-CEM |
CC90 |
< |
3.0 |
uM |
Cytotoxicity against human CEM cells assessed as inhibition of mitochondrial DNA synthesis |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
50000.0 |
nM |
Cytotoxicity against human erythroid progenitor cells after 14 to 16 days by colony formation assay |
CHEMBL1629705 |
| ADMET |
CC50 |
> |
50000.0 |
nM |
Cytotoxicity against human myeloid progenitor cells after 14 to 16 days by colony formation assay |
CHEMBL1629705 |
| Hepatitis C virus |
EC50 |
= |
48.0 |
nM |
Antiviral activity against HCV subtype 1b by replicon assay |
CHEMBL3792304 |
| Genome polyprotein |
Ki |
= |
1500.0 |
nM |
Radiolabeled Nucleotide Incorporation Assay: To measure inhibition of the enzymatic activity of the HCV NS5B RNA-dependent RNA polymerase by the nucleoside triphosphate compounds of the present invention, a radiolabeled nucleotide incorporation assay was used. This assay is a modified version of the assay described in International Publication No. WO2002/057287. Briefly, 50 uL reactions containing 20 mM HEPES (pH 7.3); 7.5 mM DTT; 20 units/ml RNasIN; 1 uM each of ATP, GTP, UTP and CTP; 20 uCi/mL [33P]-CTP; 10 mM MgCl; 60 mM NaCl; 100 ug/ml BSA; 0.021 uM DCoH heteropolymer RNA template; and 5 nM NS5B (1b-BKDelta55) enzyme are incubated at room temperature for 1 hour. The assay is then terminated by the addition of 500 mM EDTA (50 uL). The reaction mixture is transferred to a Millipore DE81 filter plate and the incorporation of labeled CTP is determined using Packard TopCount. Compound IC50 values can then be calculated from experiments with 10 serial 3-fold dilutions of the inhibitor in duplicate. |
CHEMBL3638459 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against HCV J6/JFH/JC-1 infected in human Huh7.5 cells assessed as inhibition of NS3/4A S282T mutant levels at 0.01 to 1 uM treated with fresh media containing compound every 2 days by Western blot method |
CHEMBL4251597 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against HCV J6/JFH/JC-1 infected in human Huh7.5 cells harboring NS3/4A S282T mutant assessed as inhibition of viral core protein levels at 0.01 to 1 uM treated with fresh media containing compound every 2 days by Western blot method |
CHEMBL4251597 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against HCV infected in human GS4.3 cells assessed as inhibition of NS3/4A levels at 0.8 uM treated with fresh media containing compound every 2 days measured after 6 days by Western blot method |
CHEMBL4251597 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against HCV infected in human GS4.3 cells assessed as inhibition of viral core protein levels at 0.8 uM treated with fresh media containing compound every 2 days measured after 6 days by Western blot method |
CHEMBL4251597 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against 22.5 to 90 IU/cell of HCV J6/JFH/JC-1 infected in human Huh7.5 cells assessed as inhibition of NS3/4A levels at 0.05 uM treated with fresh media containing compound every 2 days by Western blot method |
CHEMBL4251597 |
| Hepatitis C virus |
Inhibition |
|
|
% |
Antiviral activity against 22.5 to 90 IU/cell of HCV J6/JFH/JC-1 infected in human Huh7.5 cells assessed as inhibition of viral core protein levels at 0.05 uM treated with fresh media containing compound every 2 days by Western blot method |
CHEMBL4251597 |
| Unchecked |
Ratio CC50/EC50 |
> |
3125.0 |
|
Selectivity index, ratio of CC50 for human Huh7.5 cells to EC50 for antiviral activity against HCV genotype 2a JFH/JC1 infected in human Huh7.5 cells |
CHEMBL4330116 |
| Unchecked |
CC50 |
> |
200000.0 |
nM |
Cytotoxicity against human Huh7.5 cells after 72 hrs by MTT assay |
CHEMBL4330116 |
| Hepatitis C virus |
EC50 |
= |
60.0 |
nM |
Antiviral activity against HCV genotype 2a JFH/JC1 infected in human Huh7.5 cells assessed as inhibition of viral RNA replication after 72 hrs by qRT-PCR analysis |
CHEMBL4330116 |
| Hepatitis C virus |
EC50 |
= |
220.0 |
nM |
Antiviral activity against HCV con1 subgenomic replicon infected in human HuH7 cells assessed as reduction in viral RNA replication by qRT-PCR analysis |
CHEMBL4393666 |
| Huh-7 |
CC50 |
> |
100000.0 |
nM |
Cytotoxicity against human HuH7 cells infected with HCV con1 subgenomic replicon assessed as reduction in cell viability measured after 3 days by CellTiter-blue cell viability assay |
CHEMBL4393666 |
| Replicase polyprotein 1ab |
Inhibition |
= |
6.51 |
% |
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate |
CHEMBL4495564 |
| SARS-CoV-2 |
Inhibition |
= |
-0.07 |
% |
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging |
CHEMBL4495565 |
| SARS-CoV-2 |
Inhibition |
= |
-0.07 |
% |
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging |
CHEMBL4495565 |
| SARS-CoV-2 |
IC50 |
> |
20000.0 |
nM |
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging |
CHEMBL4651402 |
| SARS-CoV-2 |
IC50 |
< |
19952.62 |
nM |
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging |
CHEMBL4651402 |
