Project: Identification of Trypanosoma cruzi inhibitors with a focus on trypanocidal compounds for treatment of chronic stage Chagas disease Probe (Project ID: 1143)


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PID:
1143
Status:
Approved Approved
Approved By:
Josh Bittker (10/24/2013)
Name:
Identification of Trypanosoma cruzi inhibitors with a focus on trypanocidal compounds for treatment of chronic stage Chagas disease
Description:
The main goal is to identify new drugs for the treatment of Chagas disease. New drugs are needed because the only two drugs currently available are only effective against the early stages of disease and have significant toxicity to the patient. No drug is available to treat the chronic stage. This assay approach is intended to select drugs that will be effective against the early stages of disease when parasites are found mainly extracellularly, but also drugs that will be effective against the chronic stage, where parasites are found inside host cells. Therefore we will select drugs that are either trypanostatic (expected to be effective in the acute phase of disease) or trypanocidal (expected to be effective against the chronic stage) with a preference for the latter.
Owner:
Broad
Date Created:
05/31/2013
Last Updated:
05/09/2014
Modified By:
dlahr

Probes


Annotations

project management

grant number MH085673-01
laboratory name Broad Institute
project lead name (244) (lcarmody) Leigh Carmody

probe

PubChem CID CID 44493436
probe report ML341

biology

biology biological process
GO biological process term parasitism
disease infectious disease
Mesh term (68014355) Chagas Disease

Biology

Biology Term Type Term Value
process GO biological process term parasitism

Experiments and steps

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Experiments

EID Experiment Name Role # Compounds ADID Assay Name
Tested Active
7521 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, DOS collection HTS primary screen primary screen 76537 4582 89 Approved Approved Cell-Based T. Cruzi Proliferation Assay By lacZ Reporter using luminescent kit readout
8088 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, Probe SAR primary screen 22315 1092
4863 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, Cherry pick 1 replicate 1 confirmatory screen 5589 4045
4864 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, cherry pick 1 lower concentration 2 uM repeat confirmatory screen 5588 1195
8087 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, DMSO cherry pick 2 confirmatory screen 800 717
8081 Approved Approved Inhibition of T.cruzi proliferation in culture Measured in Cell-Based System Using Plate Reader - 2138-01_Inhibitor_Dose_DryPowder_Activity_Set2 confirmatory screen 245 215
8071 Approved Approved Luminescence Cell-Based/Microorganism Dose Confirmation screen to Identify Inhibitors of T.Cruzi Replication and infection, Dry powders confirmatory screen 58 27
4866 Approved Approved Luminescence Cell-Based Dose Response Screen to Identify Cytotoxic Compounds of NIH3T3 cells, cherry pick 1 retest at higher concentration 25 uM compound toxicity screen 5589 3102 8266 Approved Approved NIH-3T3 90 hour cytotoxicity luminescent assay using Cell titer glo
4865 Approved Approved Luminescence Cell-Based Dose Response Screen to Identify Cytotoxic Compounds of NIH3T3 cells, cherry pick 1 compound toxicity screen 5589 780
8084 Approved Approved Luminescence Cell-Based Dose Response Screen to Identify Cytotoxic Compounds of NIH3T3 cells, probe SAR compound toxicity screen 245 20
8086 Approved Approved Luminescence Cell-Based Dose Response Screen to Identify Cytotoxic Compounds of NIH3T3 cells, DMSO Cherry pick 2 compound toxicity screen 191 29
8070 Approved Approved Luminescence Cell-Based Dose Response Screen to Identify Cytotoxic Compounds of NIH3T3 cells, Dry powders compound toxicity screen 58 2
8074 Approved Approved Inhibition of intracellular CAI/72 strain of Trypanosoma cruzi in bovine embryo skeletal muscle cells by high content imaging, probe series SAR alternative assay readout 64 28 8317 Approved Approved Fluorescence DNA parasite and host cell microscopy 72 hour microscopy counting assay to measure inhibition of intracellular T. cruzi pasasites
5915 Approved Approved L-6 rat myocyte cell toxicity counterscreen, DMSO cherry pick compound toxicity screen 20 5 8316 Approved Approved L6 myocyte 70 hour cytotoxicity luminescent assay using Alamar blue
8079 Approved Approved L-6 rat myocyte cell toxicity counterscreen, dry powders compound toxicity screen 8 0
5911 Approved Approved Secondary assay in alternate L6 cell line measured by absorbance of LacZ reporter substrate, DMSO cherry pick alternative confirmatory screen 20 5 5916 Approved Approved Cell-Based T. Cruzi lacZ reporter infection Assay in L-6 cells measured by absorbance
8076 Approved Approved Secondary assay in alternate L6 cell line measured by absorbance of LacZ reporter substrate, Dry powders alternative confirmatory screen 8 8
5912 Approved Approved Inhibition of Plasmodium falciparum NF54 erythrocyte infection, DMSO cherry pick alternative organism screen 20 5 5917 Approved Approved Inhibition of Plasmodium falcipirum NF54 in host human erythrocytes
8075 Approved Approved Inhibition of Plasmodium falciparum NF54 erythrocyte infection, dry powder cherry pick alternative organism screen 8 0
5914 Approved Approved T. brucei axenic culture proliferation assay, DMSO cherry pick alternative organism screen 20 2 5919 Approved Approved Trypanosoma brucei rhodesiense axenic culture proliferation assay
8078 Approved Approved T. brucei axenic culture proliferation assay, dry powder cherry pick alternative organism screen 8 2
5913 Approved Approved Inhibition of L. donovani axenic amastigotes, DMSO cherry pick alternative organism screen 20 0 5918 Approved Approved Cell-Based L. donovani proliferation microscopy assay
8077 Approved Approved Inhibition of L. donovani axenic amastigotes, dry powder cherry pick alternative organism screen 8 0
8082 Approved Approved J774 cell trypanosome infection assay with compound withdrawal to determine trypanostatic or trypanocidal mode of action, probe replicate 2 alternative assay type 11 11 8181 Approved Approved High Content Imaging Assay to Measure T. cruzi CAI/72 Strain in J774
8083 Approved Approved J774 cell trypanosome infection assay with compound withdrawal to determine trypanostatic or trypanocidal mode of action, probe replicate 1 alternative assay type 11 11
8073 Approved Approved BESM cell trypanosome infection assay with compound withdrawal to determine trypanostatic or trypanocidal mode of action, probe series dry powder replicate 1 alternative assay type 10 10 8179 Approved Approved Microscopy based T. cruzi infection assay in BESM cells with long-term outgrowth after compound withdrawal
8072 Approved Approved BESM cell trypanosome infection assay with compound withdrawal to determine trypanostatic or trypanocidal mode of action, probe series dry powder replicate 2 alternative assay type 10 10
8085 Approved Approved Inhibition of Trypanosoma cruzi Cruzain Measured using AMC-peptide; probe SAR alternative assay format 5 0 8180 Approved Approved Biochemical Assay of Cruzain (T. cruzi) Inhibition
8080 Approved Approved Inhibition of Trypanosoma cruzi Cruzain Measured using AMC-peptide; probe series dry powder alternative assay format 1 1

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