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BioAssay: AID 1674

Broad Institute MLPCN Ras Selective Lethality Project

Brent Stockwell, Columbia University, 614 Fairchild Center, MC 2406, 1212 Amesterdam Ave, New York, NY 10027, bs2189@columbia.edu, 212.854.2948 ..more
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Probe(1)
 
 
Active(1)
 
 
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Probe(1)
 
 
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 Related BioAssays
AID: 1674
Data Source: Broad Institute (2013)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-04-10
Modify Date: 2013-03-11

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compound: Chemical Probe: 1    Active: 1
Related Experiments
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AIDNameTypeComment
1554MLPCN Ras selective lethality-BJeLR viabilityScreeningdepositor-specified cross reference: 303344 hts compounds at singlepoint in BJeLR viability measuring activity set 1
1933Luminescence Cell-Based Dose Response HTS to Identify Compounds Cytotoxic to BJ-TERT RAS-Independent FibroblastConfirmatorydepositor-specified cross reference: 1155 cherrypick compounds at dose in BJ-TERT viability measuring activity set 1
1934Luminescence Cell-Based Dose Response HTS to Identify Compounds Cytotoxic to DRD Non-Viral Oncogenic FibroblastConfirmatorydepositor-specified cross reference: 1155 cherrypick compounds at dose in DRD viability measuring activity set 1
1935Luminescence Cell-Based Dose Response HTS to Identify Compounds Cytotoxic to BJ-TERT-LT-ST RAS-Independent FibroblastConfirmatorydepositor-specified cross reference: 1155 cherrypick compounds at dose in BJ-TERT-LT-ST viability measuring activity set 1
1936Luminescence Cell-Based Dose Confirmation HTS to Identify Compounds Cytotoxic to BJeLR RAS-Dependent FibroblastConfirmatorydepositor-specified cross reference: 1155 cherrypick compounds at dose in BJeLR viability measuring activity set 1
2275Luminescence Cell-Based Primary HTS to Measure Viability of BJeLR cellsScreeningdepositor-specified cross reference: 30036 hts compounds at singlepoint in BJeLR viability measuring activity set 1
2607Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to Non-Viral Oncogenic DRD Fibroblasts.Confirmatorydepositor-specified cross reference: 14 drypowder compounds at dose in DRD AlamarBlue viability measuring activity set 1
2608Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJeLR FibroblastsConfirmatorydepositor-specified cross reference: 14 drypowder compounds at dose in BJeLR AlamarBlue viability measuring activity set 1
2609Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJ-TERT-LT-ST Fibroblasts.Confirmatorydepositor-specified cross reference: 14 drypowder compounds at dose in BJ-TERT-LT-ST AlamarBlue viability measuring activity set 1
2610Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJeLR FibroblastConfirmatorydepositor-specified cross reference: 435 cherrypick compounds at dose in BJeLR AlamarBlue viability measuring activity set 1
2611Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJ-TERT Fibroblasts.Confirmatorydepositor-specified cross reference: 14 drypowder compounds at dose in BJ-TERT AlamarBlue viability measuring activity set 1
2631Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJ-TERT-LT-ST FibroblastConfirmatorydepositor-specified cross reference: 435 cherrypick compounds at dose in BJ-TERT-LT-ST AlamarBlue viability measuring activity set 1
2633Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to Non-Viral Oncogenic DRD FibroblastConfirmatorydepositor-specified cross reference: 73 cherrypick compounds at dose in DRD AlamarBlue viability measuring activity set 1
2635Fluorescence Cell-Based Dose Response to Characterize Compounds Cytotoxic to RAS-Dependent BJ-TERT FibroblastConfirmatorydepositor-specified cross reference: 73 cherrypick compounds at dose in BJ-TERT AlamarBlue viability measuring activity set 1
493045Primary viability screen, Ras selective lethality- BJeLR cells Measured in Cell-Based System Using Plate Reader - 2013-05_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: 20 drypowder compounds at dose in BJeLR AlamarBlue viability measuring activity set 3
493049Viability secondary screen, Ras selective lethality- DRD cells Measured in Cell-Based System Using Plate Reader - 2013-08_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: 20 drypowder compounds at dose in DRD AlamarBlue viability measuring activity set 3
493050Viability secondary screen, Ras selective lethality- DRD cells Measured in Cell-Based System Using Plate Reader - 2013-08_Inhibitor_Dose_DryPowder_Activity_Set2Confirmatorydepositor-specified cross reference: 31 drypowder compounds at dose in DRD AlamarBlue viability measuring activity set 2
493051Viability counterscreen, Ras selective lethality- BJeH cells Measured in Cell-Based System Using Plate Reader - 2013-06_Inhibitor_Dose_DryPowder_Activity_Set2Confirmatorydepositor-specified cross reference: 31 drypowder compounds at dose in BJ-TERT AlamarBlue viability measuring activity set 2
493052Viability counterscreen, Ras selective lethality- BJeHLT cells Measured in Cell-Based System Using Plate Reader - 2013-07_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: 20 drypowder compounds at dose in BJ-TERT-LT-ST AlamarBlue viability measuring activity set 3
493053Primary viability screen, Ras selective lethality- BJeLR cells Measured in Cell-Based System Using Plate Reader - 2013-05_Inhibitor_Dose_DryPowder_Activity_Set2Confirmatorydepositor-specified cross reference: Primary viability screen, Ras selective lethality- BJeLR cells Measured in Cell-Based System Using P
493054Viability counterscreen, Ras selective lethality- BJeH cells Measured in Cell-Based System Using Plate Reader - 2013-06_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: 20 drypowder compounds at dose in BJ-TERT AlamarBlue viability measuring activity set 3
493093Viability counterscreen, Ras selective lethality- BJeHLT cells Measured in Cell-Based System Using Plate Reader - 2013-07_Inhibitor_Dose_DryPowder_Activity_Set2Confirmatorydepositor-specified cross reference: 31 drypowder compounds at dose in BJ-TERT-LT-ST AlamarBlue viability measuring activity set 2
540314Viability counterscreen, Ras selective lethality- BJeHLT cells Measured in Cell-Based System Using Plate Reader - 2013-07_Inhibitor_Dose_DryPowder_Activity_Set4Confirmatorydepositor-specified cross reference
540315Viability secondary screen, Ras selective lethality- DRD cells Measured in Cell-Based System Using Plate Reader - 2013-08_Inhibitor_Dose_DryPowder_Activity_Set4Confirmatorydepositor-specified cross reference
540316Viability counterscreen, Ras selective lethality- BJeH cells Measured in Cell-Based System Using Plate Reader - 2013-06_Inhibitor_Dose_DryPowder_Activity_Set4Confirmatorydepositor-specified cross reference
540318Primary viability screen, Ras selective lethality- BJeLR cells Measured in Cell-Based System Using Plate Reader - 2013-05_Inhibitor_Dose_DryPowder_Activity_Set4Confirmatorydepositor-specified cross reference
652070HT29 HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-21_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: Extended probe characterization
652072LOX IMVI HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-22_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: Extended probe characterization
Description:
Broad Institute of MIT and Harvard, Cambridge MA

NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number MH084117-01

Internal Project ID: 2013

Keywords: Ras, apoptosis, cancer, VDAC, oxidative cell death

Primary Collaborators:

Brent Stockwell, Columbia University, 614 Fairchild Center, MC 2406, 1212 Amesterdam Ave, New York, NY 10027, bs2189@columbia.edu, 212.854.2948

Dan Zaharevitz, NCI Science Officer, zaharevd@mail.nih.gov

Project Overview:

The goal of the project is to identify small molecules in the MLSMR and related compound synthesized through follow-up chemistry that are selectively lethal to tumor cells expressing RAS oncogenes. These probes will not necessarily interact with the RAS pathway, but may induce cell death by affecting cellular processes that, in conjunction with the activation of the RAS pathway, selectively kill the tumor cells.

Primary Assay Summary:

Name: BJeLR viability

Internal ID: 2013-01

Cell viability of BJeLR (BJ fibroblasts transformed with hTERT, genomic SV40 LT and ST oncoproteins, and oncogenic HRASV12). Using CellTiterGlo, which measures the amount of intracellular ATP from living cells, the total amount of viable cells can be measured by luminescence readout. Cells are treated with compounds for 48 hours to allow detection of compounds that may be slower-acting.
Expected Outcome: Compounds that are toxic to these transformed fibroblasts, either selectively due to the HRAS oncogene or due to nonspecific toxicity, will cause a loss of luminescence signal due to fewer live cells. Specificity will be determined in future counterscreening.
Comment
The following compounds [SID] were purchased or synthesized for this project:
87692468 87692469 87692470 87692471 87692472 87692473 87692474 87692475 87692476 87692477 87692478 87692479 87692480 87692481
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 2
MLP Probe ML# for probe 1: ML162
PubChem Substance ID (SID) for probe 1: 87692475
PubChem Compound ID (CID) for probe 1: 3689413
IC50/EC50 (nM) for probe 1: 25
Target for probe 1: BJeLR (HRASV12)
Disease relevance for probe 1: Cancer
Anti-target for probe 1: BJeH-LT (w/o HRASV12)
Fold selectivity for probe 1: 23
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK55069/ (ID: 2377624)
Grant number for probe 1: MH084117-01
MLP Probe ML# for probe 2: ML210
PubChem Substance ID (SID) for probe 2: 103023280
PubChem Compound ID (CID) for probe 2: 49766530
Probe type for probe 2: Inhibitor
IC50/EC50 (nM) for probe 2: 71
Target for probe 2: BJeLR (HRASV12)
Disease relevance for probe 2: Cancer
Anti-target for probe 2: BJeH-LT (without HRASV12)
Fold selectivity for probe 2: 4
NCBI Book chapter link for probe 2: http://www.ncbi.nlm.nih.gov/books/NBK98919/ (ID: 2961564)
Grant number for probe 2: MH084117-01
NCBI Book chapter title for probe 1: Screen for RAS-Selective Lethal Compounds and VDAC Ligands - Probe 1
NCBI Book chapter title for probe 2: Screen for RAS-Selective Lethal Compounds and VDAC Ligands - Probe 2
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1ML_NUMML number assigned to compound.String
Additional Information
Grant Number: MH084117-01

Data Table (Concise)
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