| Vero |
IC50 |
= |
0.5 |
nM |
Anti-Herpes simplex virus type-1 activity in vero cells using plaque inhibition assay |
CHEMBL1132358 |
| ADMET |
Binding energy |
= |
8.2 |
kCal mol-1 |
Binding energy by using the equation deltaG obsd = -RT ln KD |
CHEMBL1122538 |
| Hepatitis C virus NS5B RNA-dependent RNA polymerase |
IC50 |
= |
22000.0 |
nM |
Inhibition HCV NS5B-mediated RNA synthesis |
CHEMBL1149159 |
| Hepatitis C virus NS5B RNA-dependent RNA polymerase |
EC50 |
|
46000.0 |
nM |
Inhibition HCV RNA replication |
CHEMBL1149159 |
| Human herpesvirus 1 |
MIC |
> |
40.0 |
ug.mL-1 |
Antiviral activity against HSV-1(KOS) strain in primary rabbit kidney (PRK) / embryonic skin-muscle (E6SM) fibroblast culture lines |
CHEMBL1126104 |
| Human herpesvirus 2 |
MIC |
> |
40.0 |
ug.mL-1 |
Antiviral activity against HSV-2(G) strain in primary rabbit kidney (PRK) / embryonic skin-muscle (E6SM) fibroblast culture lines |
CHEMBL1126104 |
| Vaccinia virus |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against vaccinia virus (VV) in primary rabbit kidney (PRK) / embryonic skin-muscle (E6SM) fibroblast culture lines |
CHEMBL1126104 |
| Vesicular stomatitis virus |
MIC |
> |
40.0 |
ug.mL-1 |
Antiviral activity against vesicular stomatitis virus (VSV) in primary rabbit kidney (PRK) / embryonic skin-muscle (E6SM) fibroblast culture lines |
CHEMBL1126104 |
| Vesicular stomatitis virus |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against vesicular stomatitis virus (VSV) in HeLa cell culture lines, |
CHEMBL1126104 |
| Human poliovirus 1 |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against polio virus type 1 in HeLa cell culture lines |
CHEMBL1126104 |
| Human coxsackievirus B4 |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against coxsackie B4 virus in HeLa cell culture lines |
CHEMBL1126104 |
| Human coxsackievirus B4 |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against coxsackie B4 in Vero cell culture lines |
CHEMBL1126104 |
| Human parainfluenza virus 3 |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against parainfluenza virus type 3 in Vero cell culture lines |
CHEMBL1126104 |
| Mammalian orthoreovirus 1 |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against reovirus type 1 in Vero cell culture lines |
CHEMBL1126104 |
| Sindbis virus |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against sindbis virus in Vero cell culture lines |
CHEMBL1126104 |
| Semliki forest virus |
MIC |
> |
100.0 |
ug.mL-1 |
Antiviral activity against semliki forest virus (SFV) in Vero cell culture lines |
CHEMBL1126104 |
| Human immunodeficiency virus 1 |
MIC |
> |
4.0 |
ug.mL-1 |
Antiviral activity against (HIV-1) in MT-4 cells Value in parentheses is inhibitory concentration for cell growth (MT-4) |
CHEMBL1126104 |
| Adenosine A1 receptor |
Ki |
= |
7120.0 |
nM |
Affinity for the Adenosine A1 receptor in the absence of GTP (A1-GTP) by using [3H]DPCPX as radioligand |
CHEMBL1128455 |
| Adenosine A1 receptor |
Ki |
= |
15200.0 |
nM |
Affinity for the Adenosine A1 receptor in the presence of GTP (A1+GTP) by using [3H]-DPCPX as radioligand |
CHEMBL1128455 |
| Rattus norvegicus |
GTP shift |
= |
2.1 |
|
GTP shift was determined in rat |
CHEMBL1128455 |
| Adenosine A1 receptor |
Ki |
= |
7120.0 |
nM |
Affinity for adenosine A1 receptor was determined, in the absence of GTP in rat cortical membrane. |
CHEMBL1130233 |
| Adenosine A1 receptor |
Ki |
= |
15200.0 |
nM |
Affinity for adenosine A1 receptor was determined, in the presence of GTP in rat brain cortex |
CHEMBL1130233 |
| Adenosine A1 receptor |
Ratio |
= |
2.1 |
|
GTP shift ratio of the apparent Ki values in the presence and absence of GTP. |
CHEMBL1130233 |
| Human immunodeficiency virus 1 |
ED50 |
> |
50.0 |
uM |
Dose required to inhibit cytopathic effect of human immunodeficiency virus replication in MT-4 cells. |
CHEMBL1124230 |
| MT4 |
CD50 |
= |
45.0 |
uM |
Cytotoxic dose required to reduce the viability of normal uninfected MT-4 cells. |
CHEMBL1124230 |
| MT4 |
Selectivity index |
< |
0.5 |
|
Ratio of CD50 to ED50 rvaluated for inhibition of HIV replication in MT-4 cells |
CHEMBL1124230 |
| Mus musculus |
Tmax |
= |
1.5 |
hr |
Tmax in C57BL/6 mouse at 0.5 umol/kg, po |
CHEMBL1153879 |
| Mus musculus |
Cmax |
= |
10100.0 |
nM |
Cmax in C57BL/6 mouse at 0.5 umol/kg, po |
CHEMBL1153879 |
| Mus musculus |
AUC |
= |
4824.0 |
ng.hr.mL-1 |
AUC in C57BL/6 mouse at 0.5 umol/kg, po |
CHEMBL1153879 |
| Mus musculus |
T1/2 |
= |
2.1 |
hr |
Half life in C57BL/6 mouse at 0.5 umol/kg, po |
CHEMBL1153879 |
| Mus musculus |
Tmax |
= |
1.5 |
hr |
Tmax in C57BL/6 mouse at 0.5 umol/kg, po assessed as transformed cordycepin levels |
CHEMBL1153879 |
| Mus musculus |
Cmax |
= |
10100.0 |
nM |
Cmax in C57BL/6 mouse at 0.5 umol/kg, po assessed as transformed cordycepin levels |
CHEMBL1153879 |
| Mus musculus |
AUC |
= |
4824.0 |
ng.hr.mL-1 |
AUC in C57BL/6 mouse at 0.5 umol/kg, po assessed as transformed cordycepin levels |
CHEMBL1153879 |
| Mus musculus |
T1/2 |
= |
2.1 |
hr |
Half life in C57BL/6 mouse at 0.5 umol/kg, po assessed as transformed cordycepin levels |
CHEMBL1153879 |
| Plasmodium falciparum (isolate K1 / Thailand) |
IC50 |
= |
4.5 |
ug.mL-1 |
Antimalarial activity against multidrug-resistant Plasmodium falciparum K1 after 24 hrs by [3H]hypoxanthine uptake |
CHEMBL1148961 |
| Unchecked |
EC50 |
= |
4100.0 |
nM |
PUBCHEM_BIOASSAY: Fluorescence Cell-Based Retest of Candida albicans Growth in the Presence of Fluconazole. (Class of assay: confirmatory) [Related pubchem assays: 2007 (Project Summary), 1979 (Primary HTS)] |
CHEMBL1201862 |
| Hepatotoxicity |
Hepatotoxicity |
|
|
|
Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans |
CHEMBL1697731 |
| Hepatotoxicity |
Hepatotoxicity |
|
|
|
Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents |
CHEMBL1697731 |
| Hepatotoxicity |
Hepatotoxicity |
|
|
|
Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents |
CHEMBL1697731 |
| Mitochondrial import inner membrane translocase subunit TIM23 |
IC50 |
= |
14000.0 |
nM |
PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS small molecule inhibitors of tim23-1 yeast via a luminescent assay. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID463212, AID463216, AID504657, AID504672] |
CHEMBL1201862 |
| ATP-dependent molecular chaperone HSP82 |
EC50 |
> |
150000.0 |
nM |
PUBCHEM_BIOASSAY: Fluorescence Cell-Based Secondary Assay to Identify Inhibitors of Resistant C. albicans Growth in the Presence of Fluconazole. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1979, AID2007] |
CHEMBL1201862 |
| Unchecked |
Potency |
|
4466.8 |
nM |
PUBCHEM_BIOASSAY: qHTS for Inhibitors of Cell Surface uPA Generation. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID493178] |
CHEMBL1201862 |
| Unchecked |
EC50 |
> |
150000.0 |
nM |
PUBCHEM_BIOASSAY: Fluorescence Cell-Based Secondary Assay for toxicity in mammalian fibroblasts. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1979, AID2007] |
CHEMBL1201862 |
| Trichomonas vaginalis |
GI |
= |
94.1 |
% |
Growth inhibition of Trichomonas vaginalis T1 at 100 uM after 24 hrs by hemocytometry |
CHEMBL2029336 |
| Unchecked |
Potency |
|
44668.4 |
nM |
PubChem BioAssay. A Quantitative High throughput Screen to Identify Chemical Modulators of PINK1 Expression. (Class of assay: confirmatory) |
CHEMBL1201862 |
| Unchecked |
Potency |
|
10000.0 |
nM |
PubChem BioAssay. qHTS Assay for Inhibitors of Hepatitis C Virus (HCV). (Class of assay: confirmatory) |
CHEMBL1201862 |
| Tyrosyl-DNA phosphodiesterase 1 |
Potency |
|
7307.8 |
nM |
PubChem BioAssay. qHTS for Inhibitors of human tyrosyl-DNA phosphodiesterase 1 (TDP1): qHTS in cells in absence of CPT. (Class of assay: confirmatory) |
CHEMBL1201862 |
| Tyrosyl-DNA phosphodiesterase 1 |
Potency |
|
8199.5 |
nM |
PubChem BioAssay. qHTS for Inhibitors of human tyrosyl-DNA phosphodiesterase 1 (TDP1): qHTS in cells in presence of CPT. (Class of assay: confirmatory) |
CHEMBL1201862 |
| Transcription factor p65 |
Inhibition |
|
|
% |
Inhibition of NFkappaB p65 nuclear translocation in mouse RAW264.7 cells after 24 hrs by DAPI staining-based laser confocal immunofluorescent microscopic analysis |
CHEMBL2390938 |
| Unchecked |
Ki |
= |
180.0 |
nM |
Displacement of [2,8-3H]-adenosine from Trypanosoma brucei AT1/P2 expressed in bloodstream stage of Trypanosoma brucei brucei B48 |
CHEMBL3108778 |
| MOLT-4 |
IC50 |
>= |
100000.0 |
nM |
Cytotoxicity against human MOLT4 cells assessed as cell viability after 72 hrs by WST-1 assay |
CHEMBL3108778 |
| Trypanosoma brucei |
IC50 |
= |
42.0 |
nM |
Trypanocidal activity against bloodstream stage of Trypanosoma brucei after 72 hrs by WST-1 assay |
CHEMBL3108778 |
| Trypanosoma brucei |
IC50 |
= |
32.0 |
nM |
Trypanocidal activity against Trypanosoma brucei |
CHEMBL3108778 |
| L929 |
IC50 |
= |
28700.0 |
nM |
Cytotoxicity against mouse L929 cells assessed as cell viability after 72 hrs by WST-1 assay |
CHEMBL3108778 |
| Trypanosoma brucei |
IC50 |
= |
1.2 |
nM |
Trypanocidal activity against bloodstream stage of Trypanosoma brucei after 72 hrs by WST-1 assay in presence of deoxycoformycin |
CHEMBL3108778 |
| MOLT-4 |
IC50 |
= |
100.0 |
nM |
Cytotoxicity against human MOLT4 cells assessed as cell viability after 72 hrs by WST-1 assay in presence of deoxycoformycin |
CHEMBL3108778 |
| Trypanosoma brucei brucei |
IC50 |
= |
30.0 |
nM |
Trypanocidal activity against bloodstream stage of Trypanosoma brucei brucei AnTat1.1E after 72 hrs by WST-1 assay |
CHEMBL3108778 |
| Adenosine deaminase |
Drug metabolism |
|
|
|
Drug metabolism in human MOLT4 cells assessed as ADA-mediated inosine metabolite formation |
CHEMBL3108778 |
| Adenosine deaminase |
Drug metabolism |
|
|
|
Drug metabolism assessed as recombinant human ADA-mediated 3'-deoxyinosine metabolite formation at 100 uM measured every 15 mins for 10 hrs by spectrophotometric analysis in presence of deoxycoformycin |
CHEMBL3108778 |
| Adenosine deaminase |
Drug metabolism |
|
|
|
Drug metabolism assessed as recombinant human ADA-mediated 3'-deoxyinosine metabolite formation at 100 uM measured every 15 mins for 10 hrs by spectrophotometric analysis |
CHEMBL3108778 |
| Trypanosoma brucei brucei |
Activity |
|
|
|
Trypanocidal activity against bloodstream stage of Trypanosoma brucei brucei AnTat1.1E after 72 hrs by WST-1 assay in presence of adenosine kinase inhibitor ABT702 |
CHEMBL3108778 |
| Trypanosoma brucei brucei |
Activity |
|
|
|
Trypanocidal activity against bloodstream stage of Trypanosoma brucei brucei AnTat1.1E infected in C57BL6J (B6) mouse assessed as reduction of parasitemia at 2 mg/kg, ip qd measured after 30 days |
CHEMBL3108778 |
| Trypanosoma brucei brucei |
Activity |
|
|
|
Trypanocidal activity against bloodstream stage of Trypanosoma brucei brucei AnTat1.1E infected in C57BL6J (B6) mouse assessed as reduction of parasitemia at 2 mg/kg, ip qd administered for 3 days measured after 40 days in presence of deoxycoformycin |
CHEMBL3108778 |
| Hepatitis C virus |
EC50 |
= |
70000.0 |
nM |
Antiviral activity against Hepatitis C virus infected in African green monkey OR6 cells after 72 hrs by luciferase reporter gene assay |
CHEMBL3352698 |
| ADMET |
CC50 |
= |
13000.0 |
nM |
Cytotoxicity against human ORL8 cells after 72 hrs by WST-1 assay |
CHEMBL3352698 |
| Unchecked |
Ratio CC50/EC50 |
= |
0.19 |
|
Selectivity index, ratio of CC50 for human ORL8 cells to EC50 for Hepatitis C virus infected in African green monkey OR6 cells |
CHEMBL3352698 |
| Leishmania donovani |
IC50 |
< |
50118.72 |
nM |
GSK_TCAKS: pIC50 Leishmania donovani Imaging: Infected Macrophages. Assay plates (384-well) were prepared by adding 250nL of compound to each well. For single shot assay, the final compound concentration was 5 uM. For potency determinations, eleven-point one in three dilution curves were generated with a top concentration of 50 uM. Two exposure images were taken for each well using 405 nm and 488 nm laser excitation. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: Percent of infected macrophage cells were reported for each well. |
CHEMBL3430912 |
| Trypanosoma cruzi |
IC50 |
= |
5011.87 |
nM |
GSK_TCAKS: pIC50 H2C9 Imaging: H9c2 Host Cardiomyocytes. H9c2 cells were seeded in T-225 flasks (225cm^2 culture surface; Corning Inc., NY, USA) in DMEM-10% FBS for 4h to allow attachment. Cells were then washed once with PBS before infection. T. cruzi trypomastigotes, collected at days 5 to 8 after infection from LLC-MK2 parasite infected cultures, were allowed to swim out for 4h at 37C from a centrifuged pellet (2,500 rpm/10 min/room temperature). Trypomastigotes were then collected and counted in a CASY Cell Counter. Trypomastigotes, in supplemented DMEM, were added to H9c2 cultures in a multiplicity of infection of 1 and incubated for 18 h. Cells were washed once with PBS before incubation of the infected H9c2 monolayer with trypsin (Life-Technologies) to detach cells from the flask. Cells were counted in a CASY Cell Counter using a 150 um capillary and their density set at 5 * 10^4 cells per mL in supplemented assay DMEM. Infected H9c2 were dispensed into 384-well poly-lysine coated assay plates at 50uL per well using a Multidrop Combi dispenser. After seeding them, the plates were incubated at 37C, 5% CO2 for 72h. Cultures were then fixed and stained by addition of 50 uL of a solution containing 8% formaldehyde and 4 uM DRAQ5 DNA dye (BioStatus, UK) per well. Plates were kept light-protected and imaged one hour later in a Perkin-Elmer Opera microscope using a 20x air objective (NA 0.4) and the following acquisition set: a 635 nm laser excitation line and a 690/50 emission detection filter for DRAQ5 detection. Five images were collected per well for reliable statistical analysis. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: Number of H9c2 Host Cardiomyocytes nuclei to determine drug-related cytotoxicity. |
CHEMBL3430912 |
| Leishmania donovani |
IC50 |
< |
50118.72 |
nM |
GSK_TCAKS: pIC50 Leishmania donovani Imaging: Amastigotes/Macrophages. Assay plates (384-well) were prepared by adding 250nL of compound to each well. For single shot assay, the final compound concentration was 5 uM. For potency determinations, eleven-point one in three dilution curves were generated with a top concentration of 50 uM. Two exposure images were taken for each well using 405 nm and 488 nm laser excitation. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: Average number of amastigotes per macrophage cell were reported for each well. |
CHEMBL3430912 |
| Leishmania donovani |
IC50 |
< |
50118.72 |
nM |
GSK_TCAKS: pIC50 Leishmania donovani Imaging: THP-1 Host Macrophages. Assay plates (384-well) were prepared by adding 250nL of compound to each well. For single shot assay, the final compound concentration was 5 uM. For potency determinations, eleven-point one in three dilution curves were generated with a top concentration of 50 uM. Two exposure images were taken for each well using 405 nm and 488 nm laser excitation. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: THP-1 cell count were reported for each well. |
CHEMBL3430912 |
| Trypanosoma brucei brucei |
IC50 |
= |
12.59 |
nM |
GSK_TCAKS: pIC50 Trypanosoma brucei viability assay using fluorescence intensity. Assay plates (1536-well) were prepared by dispensing 25nL of compound solution per well using an Echo acoustic dispenser (Labcyte). For single shot assays the final compound concentration was 4.2uM. For potency determinations, eleven-point one in three dilution curves were generated and the top concentration was 42uM. Plates were incubated for 2h at room temperature and resorufin fluorescence was determined using a PerkinElmer ViewLux plate reader (excitation at 528 nm and emission at 590 nm). |
CHEMBL3430912 |
| Trypanosoma brucei brucei |
IC50 |
= |
10.0 |
nM |
GSK_TCAKS: pIC50 Trypanosoma brucei viability assay using luminiscence. Assay plates (1536-well) were prepared. T. brucei cultures were harvested and counted in a CASY cell counter. A parasite suspension was prepared at a final concentration of 5 * 10^4 cells/mL in complete HMI9 medium and 6uL was dispensed to all wells containing compounds using a Multidrop Combi dispenser. 6uL of HMI9 media with 0.4% DMSO were dispensed to control columns. Plates were incubated for 24 h at 37C, 5% CO2 then tempered for 10 min at room temperature. ATP content was quantified by adding 4 uL of CellTiter-Glo Reagent (Promega) according to the manufacturer's instructions. Luminescence was measured using a ViewLux. |
CHEMBL3430912 |
| HepG2 |
IC50 |
< |
100000.0 |
nM |
GSK_TCAKS: pIC50 HepG2 human cell line viability assay using luminiscence. Actively growing HepG2 cells were removed from a T-175 TC flask using 5mL Eagle's MEM (containing 10% FBS, 1% NEAA, 1% penicillin/streptomycin) and dispersed in the medium by repeated pipetting. Seeding density was checked to ensure that new mono-layers were not more than 50% confluent at the time of harvesting. Cell suspension was added to 500 mL of the same medium at a final density of 1.2 * 10^5 cells/mL. This cell suspension was dispensed (25 uL, 3000 cells per well) into 384-well clear-bottom plates using a Multidrop Combi dispenser. Prior to addition of the cell suspension, the screening compounds (250 nL) were pre-dispensed into the plates with an Echo liquid handler. Plates were incubated for 48 h at 37C, 5% CO2. After incubation, plates equilibrated at room temperature for 30 min before proceeding to develop the luminescent signal. The signal developer, CellTiter-Glo Reagent, was allowed to equilibrate at room temperature for 30 min and added to the plates (25uL per well) using a Multidrop Combi dispenser. Plates were left for 10 min at room temperature for stabilization and then read using a ViewLux. |
CHEMBL3430912 |
| Trypanosoma cruzi |
IC50 |
= |
1122.02 |
nM |
GSK_TCAKS: pIC50 Trypanosoma cruzi viability assay using beta-GAL activity. This assay was run at single shot at 5uM compound concentration per well. The biological reagents consisted of NIH-3T3 host cells and trypomastigotes parasitic cells; both cell types were set to a 3.3 * 10^5 cells/mL dilution in assay DMEM by means of a CASY cell counter device using a 60um capillary. 6 uL of the mixture were dispensed per well (about 1 * 10^3 host-cells and 1 * 10^3 parasites) with a Multidrop Combi dispenser. Previously, a solution of 1.67 * 10^5 trypomastigotes per mL in assay DMEM had been prepared and 6uL per well dispensed in the allotted control columns that defined 100% inhibition. The 0% inhibition of parasitic growth control was obtained by leaving the assay mixture untreated in its corresponding plate columns. In all wells, the percentage of DMSO never exceeded 0.5%. Plates incubated for four days at 37C, 5% CO2. The substrate used for the assay fluorescence intensity (FLINT) readout was resorufin-beta-D-galactopiranoside (Sigma-Aldrich) at 5uM per well. It was diluted in PBS supplemented with the soft detergent Igepal (Fluka). Upon addition to the plates, the substrate solution was incubated for 4h at room temperature and the signal read with the EnVision microtiter plate reader (Perkin-Elmer) using the corresponding set of filters (excitation/emission at 531/595nm). |
CHEMBL3430912 |
| NIH3T3 |
IC50 |
< |
50118.72 |
nM |
GSK_TCAKS: pIC50 NIH 3T3 cell line viability assay using luminiscence. Tissue culture surface treated assay plates (1536-well) were used. 5uL of a 2 * 10^5 cells per mL solution were dispensed per well (~10^3 host cells), into plates already containing compounds which had been pre-dispensed. The 100% cells survival control was determined exposing the host-cells to a 0.5% DMSO concentration, whereas the 100% toxicity control was achieved by seeding the cells in presence of Amphotericin B at 50uM. Plates were incubated for four days at 37C, 5% CO2. The assay readout was developed by addition of 5uL of CellTiter-Glo Reagent following the manufacturer's instructions. Luminiscence was measured using a ViewLux. |
CHEMBL3430912 |
| Trypanosoma cruzi |
IC50 |
= |
1995.26 |
nM |
GSK_TCAKS: pIC50 Trypanosoma cruzi Imaging: Infected Cells. H9c2 cells were seeded in T-225 flasks (225cm^2 culture surface; Corning Inc., NY, USA) in DMEM-10% FBS for 4h to allow attachment. Cells were then washed once with PBS before infection. T. cruzi trypomastigotes, collected at days 5 to 8 after infection from LLC-MK2 parasite infected cultures, were allowed to swim out for 4h at 37C from a centrifuged pellet (2,500 rpm/10 min/room temperature). Trypomastigotes were then collected and counted in a CASY Cell Counter. Trypomastigotes, in supplemented DMEM, were added to H9c2 cultures in a multiplicity of infection of 1 and incubated for 18 h. Cells were washed once with PBS before incubation of the infected H9c2 monolayer with trypsin (Life-Technologies) to detach cells from the flask. Cells were counted in a CASY Cell Counter using a 150 um capillary and their density set at 5 * 10^4 cells per mL in supplemented assay DMEM. Infected H9c2 were dispensed into 384-well poly-lysine coated assay plates at 50uL per well using a Multidrop Combi dispenser. After seeding them, the plates were incubated at 37C, 5% CO2 for 72h. Cultures were then fixed and stained by addition of 50 uL of a solution containing 8% formaldehyde and 4 uM DRAQ5 DNA dye (BioStatus, UK) per well. Plates were kept light-protected and imaged one hour later in a Perkin-Elmer Opera microscope using a 20x air objective (NA 0.4) and the following acquisition set: a 635 nm laser excitation line and a 690/50 emission detection filter for DRAQ5 detection. Five images were collected per well for reliable statistical analysis. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: percentage of infected cells per well as a second infection marker. |
CHEMBL3430912 |
| Sterol 14-alpha demethylase |
IC50 |
< |
100000.0 |
nM |
GSK_TCAKS: pIC50 CYP51 from Trypanosoma cruzi. |
CHEMBL3430912 |
| Trypanosoma cruzi |
IC50 |
= |
1258.93 |
nM |
GSK_TCAKS: pIC50 Trypanosoma cruzi Imaging: Amastigotes/Cell. H9c2 cells were seeded in T-225 flasks (225cm^2 culture surface; Corning Inc., NY, USA) in DMEM-10% FBS for 4h to allow attachment. Cells were then washed once with PBS before infection. T. cruzi trypomastigotes, collected at days 5 to 8 after infection from LLC-MK2 parasite infected cultures, were allowed to swim out for 4h at 37C from a centrifuged pellet (2,500 rpm/10 min/room temperature). Trypomastigotes were then collected and counted in a CASY Cell Counter. Trypomastigotes, in supplemented DMEM, were added to H9c2 cultures in a multiplicity of infection of 1 and incubated for 18 h. Cells were washed once with PBS before incubation of the infected H9c2 monolayer with trypsin (Life-Technologies) to detach cells from the flask. Cells were counted in a CASY Cell Counter using a 150 um capillary and their density set at 5 * 10^4 cells per mL in supplemented assay DMEM. Infected H9c2 were dispensed into 384-well poly-lysine coated assay plates at 50uL per well using a Multidrop Combi dispenser. After seeding them, the plates were incubated at 37C, 5% CO2 for 72h. Cultures were then fixed and stained by addition of 50 uL of a solution containing 8% formaldehyde and 4 uM DRAQ5 DNA dye (BioStatus, UK) per well. Plates were kept light-protected and imaged one hour later in a Perkin-Elmer Opera microscope using a 20x air objective (NA 0.4) and the following acquisition set: a 635 nm laser excitation line and a 690/50 emission detection filter for DRAQ5 detection. Five images were collected per well for reliable statistical analysis. Automated image analysis was performed with a script developed on Acapella High Content Imaging and Analysis Software (PerkinElmer). Output: number of amastigotes per cell as infection level measurement. |
CHEMBL3430912 |
| Leishmania donovani |
IC50 |
< |
50118.72 |
nM |
GSK_TCAKS: pIC50 Leishmania donovani viability assay using fluorescence intensity. Assay plates (1536-well) were prepared by adding 30nL per well of compound. For single shot assay, the final compound concentration was 5uM. For potency determinations, eleven-point one in three dilution curves were generated with a top concentration of 50uM. Briefly, eGFP LdBOB axenic amastigotes were harvested, fixed and counted in a CASY cell counter (Roche-Applied Science). A final concentration of 1.5 * 10^5 cells per well were prepared in amastigote media containing 500 U/mL penicillin/streptomycin (Invitrogen) and 6uL was dispensed to each experimental well using a Multidrop Combi dispenser (Thermo Scientific). 6uL of assay media was dispensed to control columns used as reference for 100% compound response. Following incubation for 72 h at 37C, 5% CO2, 2 uL of resazurin was added to each well at a final concentration of 0.5 mM in phosphate buffered saline (PBS) with IGEPAL (Sigma-Aldrich), 0.05% (v/v). The plates were incubated for 4 h at room temperature and resorufin fluorescence was detected using a PerkinElmer EnVision plate reader with excitation at 528 nm and emission at 590 nm. |
CHEMBL3430912 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated TNF-alpha production at 1 to 10 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis |
CHEMBL3632615 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated TNF-alpha production at 0.5 to 5 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis in presence of adenosine |
CHEMBL3632615 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated TNF-alpha production at 0.5 to 5 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis in presence of HEA |
CHEMBL3632615 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated PGE2 production at 1 to 10 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis |
CHEMBL3632615 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated PGE2 production at 0.5 to 5 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis in presence of adenosine |
CHEMBL3632615 |
| Toll-like receptor 4 |
Inhibition |
|
|
% |
Inhibition of TLR4-mediated NF-kappaB signaling pathway in BALB/c mouse RAW264.7 cells assessed as suppression of LPS-stimulated PGE2 production at 0.5 to 5 ug/ml preincubated for 1 hr followed by LPS challenge measured after 6 hrs by immunoblot analysis in presence of HEA |
CHEMBL3632615 |
| SARS-CoV-2 |
Inhibition |
= |
14.13 |
% |
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging |
CHEMBL4303101 |
| Trypanosoma cruzi |
EC50 |
= |
2510.0 |
nM |
Antiparasitic activity against Trypanosoma cruzi Tulahuen CL2 intracellular amastigotes expressing beta-galactosidase infected in human MRC5 SV2 cells after 7 days by chlorophenol red beta-D-galactopyranoside-based spectrophotometric analysis |
CHEMBL4382200 |
| Unchecked |
EC50 |
> |
64000.0 |
nM |
Cytotoxicity against human MRC5 SV2 cells assessed as reduction in cell viability after 3 days resazurin-based fluorimetric assay |
CHEMBL4382200 |
| ADMET |
Ratio EC50 |
> |
25.0 |
|
Therapeutic index, ratio EC50 for human MRC5 SV2 cells to EC50 for Trypanosoma cruzi Tulahuen CL2 intracellular amastigotes |
CHEMBL4382200 |
| Replicase polyprotein 1ab |
Inhibition |
= |
19.48 |
% |
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate |
CHEMBL4495564 |
| Replicase polyprotein 1ab |
Inhibition |
= |
16.8 |
% |
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate |
CHEMBL4495564 |
| SARS-CoV-2 |
Inhibition |
= |
0.0 |
% |
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 |
= |
0.03 |
% |
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 |
= |
0.03 |
% |
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 |
= |
0.0 |
% |
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 |
