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BioAssay: AID 449775

Summary of Assays used to Identify Novel Compounds That Inhibit Mycobacterium Tuberculosis in 7H9 Media with Glycerol

With approximately two billion people who have been exposed to Mycobacterium tuberculosis (M.tb) world-wide, tuberculosis has been declared a global health emergency by the WHO. In 2008, there were 9.4 million new cases of tuberculosis and approximately 2 million deaths associated with the disease, representing a nearly 10% increase in incidence since 2006. Of particular concern is the emergence more ..
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AID: 449775
Data Source: Southern Research Specialized Biocontainment Screening Center (TB_Inh_Sum)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-07-26
Modify Date: 2012-03-24
Depositor Specified Assays
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AIDNameTypeComment
449762High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Mediaconfirmatoryprimary & confirmatory screen (w/Glycerol)
493198High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compoundsconfirmatoryconfirmatory screen (w/Glycerol)
504556High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (2)confirmatoryconfirmatory screen (w/Glycerol)
504646High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (3)confirmatoryconfirmatory screen (w/Glycerol)
504857High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (4)confirmatoryconfirmatory screen (w/Glycerol)
504897High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (6)confirmatoryconfirmatory screen (w/Glycerol)
504903High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (5)confirmatoryconfirmatory screen (w/Glycerol)
588447High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (8)confirmatoryconfirmatory screen (w/Glycerol)
602435High Throughput Screening Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in 7H9 Media using Purified and Synthesized Compounds (9)confirmatoryconfirmatory screen (w/Glycerol)
449764A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerolconfirmatorycounter screen (No Glycerol)
493181A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compoundsconfirmatorycounter screen (No Glycerol)
504564A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (2)confirmatorycounter screen (No Glycerol)
504645A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (3)confirmatorycounter screen (No Glycerol)
504860A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (4)confirmatorycounter screen (No Glycerol)
504898A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (5)confirmatorycounter screen (No Glycerol)
504901A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (6)confirmatorycounter screen (No Glycerol)
588437A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (7)confirmatorycounter screen (No Glycerol)
602437A High Throughput Confirmatory Assay used to Identify Novel Compounds that Inhibit Mycobacterium Tuberculosis in the absence of Glycerol using Purified and Synthesized Compounds (8)confirmatorycounter screen (No Glycerol)
435019A Cell Based Secondary Assay To Explore Cytotoxicity of Compounds that Inhibit Mycobacterium TuberculosisconfirmatoryVero Cytotox
504335A Cell Based Secondary Assay To Explore Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis.confirmatoryVero Cytotox
504562A Cell Based Secondary Assay To Explore Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (2)confirmatoryVero Cytotox
504684A Cell Based Secondary Assay To Explore Vero Cell Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (3)confirmatoryVero Cytotox
504854A Cell Based Secondary Assay To Explore Vero Cell Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (4)confirmatoryVero Cytotox
504909A Cell Based Secondary Assay To Explore Vero Cell Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (5)confirmatoryVero Cytotox
588445A Cell Based Secondary Assay To Explore Vero Cell Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (6)confirmatoryVero Cytotox
602431A Cell Based Secondary Assay To Explore Vero Cell Cytotoxicity of Purified and Synthesized Compounds that Inhibit Mycobacterium Tuberculosis (8)confirmatoryVero Cytotox
504642A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without GlycerolconfirmatoryHepG2 Cytotox
504682A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (2)confirmatoryHepG2 Cytotox
504853A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (3)confirmatoryHepG2 Cytotox
504910A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (4)confirmatoryHepG2 Cytotox
588441A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (5)confirmatoryHepG2 Cytotox
602432A Cell Based Secondary Assay to Explore Cytotoxicity in HepG2 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (6)confirmatoryHepG2 Cytotox
504640A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without GlycerolconfirmatoryTHP1 Cytotox
504683A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (2)confirmatoryTHP1 Cytotox
504852A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (3)confirmatoryTHP1 Cytotox
504911A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (4)confirmatoryTHP1 Cytotox
588443A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (5)confirmatoryTHP1 Cytotox
602433A Cell Based Secondary Assay to Explore Cytotoxicity in THP-1 Cells of Compounds that Modulate Mycobacterium tuberculosis in Media Containing Glycerol versus Media without Glycerol (6)confirmatoryTHP1 Cytotox
Description:
Southern Research's Specialized Biocontainment Screening Center (SRSBSC)
Southern Research Institute (Birmingham, Alabama)
NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Assay Provider: Dr. William Bishai, Johns Hopkins University Tuberculosis Research Center
Award: 1 R03 MH084877-01A1

With approximately two billion people who have been exposed to Mycobacterium tuberculosis (M.tb) world-wide, tuberculosis has been declared a global health emergency by the WHO. In 2008, there were 9.4 million new cases of tuberculosis and approximately 2 million deaths associated with the disease, representing a nearly 10% increase in incidence since 2006. Of particular concern is the emergence of multiple drug resistant (MDR) and extremely drug resistant (XDR) strains for which there are few, if any effective treatments. In 2008, MDR and XDR-TB accounted for 0.5 million deaths globally. The emergence of these resistant strains is underscoring the need for new drugs that can combat M.tb.

Primary and Confirmatory screens were developed to screen large compound libraries in a synthetic lethality, 384-well format high throughput screen in BSL-3 containment at Southern Research Institute. 14,995 compounds inhibiting Mtb by 70.31% (3 standard deviations greater than the mean of the compound population) were classified as active in the primary screen yielding a high hit rate. When making selections for follow-up, previously pursued compounds and analogs of know inhibitors were excluded. Pipeline Pilot's "Diverse Molecule" component was used to select 2500 diverse substances from the remaining set. Of those 2,262 were available for continuation in the screening process.

In the confirmatory screen dose response data was collected in both the presence and absence of glycerol to identify those compounds that may be glycerol dependent inhibitors. Counter screens for cytotoxicity in three cell lines were also included to further define compounds tested.
Additional Information
Grant Number: 1 R03 MH084877-01A1

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