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BioAssay: AID 652114

Broad Institute MLPCN HRAS target ID Inhibitor Probe Project

Brent Stockwell,Columbia University,614 Fairchild Center, MC 2406, 1212 Amsterdam Ave, New York, NY 10027,bs2198@columbia.edu,212-854-2948 ..more
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AID: 652114
Data Source: Broad Institute (2156_Inhibitor_Project)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2013-03-15
Modify Date: 2013-09-24
Target
Related Experiments
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AIDNameTypeComment
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: 10 DryPowder compounds at Dose in 2156-21 21 HT-29 Apoptosis measuring Activity
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: 10 DryPowder compounds at Dose in 2156-22 22 LOX IMVI Apoptosis measuring Activity
652139HRas Target ID Cytotoxicity multiple timepoints Cell Titer Glo Measured in Cell-Based SystemOtherdepositor-specified cross reference
652143HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7Otherdepositor-specified cross reference
652144HRas Target ID Cytotoxicity Multiple Timepoints Alamar BlueOtherdepositor-specified cross reference
720598HT-29 HRas Target ID Cytotoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-05_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720599CCRF CEM HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-19_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference: 10 drypowder compounds at dose
720600SNB-19 HRAS Target ID Cytotoxicity Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-10_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720601C2C12 HRAS Target ID Cytotoxicity Mulitlpe Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-18_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720602LOX IMVI HRas Target ID Cytoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-07_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720603C2C12 HRAS Target ID Cytotoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-17_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720604HUVEC HRas Target ID Cytotoxicity multiple timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-28_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720605U-251 HRAS Target ID Cytotoxicity Mulitlpe Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-16_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720606LOX IMVI HRas Target ID Cytotoxicity at Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-08_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720607CCRF CEM HRas Target ID Cytotoxicity multiple timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-01_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720608SR HRAS Target ID Cytotoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-13_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720609HeLa HRas Target ID Cytotoxicity at Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-03_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720610HeLa HRas Target ID Cytotoxicity at Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-04_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720611SNB-19 HRas Target ID Cytotoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-09_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720612HUVEC HRas Target ID Cytotoxicity multiple timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-29_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720613SNB-75 HRAS Target ID Cytotoxicity Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-12_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720614SNB19 HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-23_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720615U251 HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-26_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720616U-251 HRAS Target ID Cytotoxicity Multiple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-15_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720617CCRF CEM HRas Target ID Cytotoxicity Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-02_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720618HeLa HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-20_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720619HT-29 HRas Target ID Cytotoxicity Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-06_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720624SNB-75 HRAS Target ID Cytotoxicity Mulitple Timepoints Cell Titer Glo Measured in Cell-Based System Using Plate Reader - 2156-11_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720625SR HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-25_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720626SR HRAS Target ID Cytotoxicity Multiple Timepoints Alamar Blue Measured in Cell-Based System Using Plate Reader - 2156-14_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720627C2C12 HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-27_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720629SNB-75 HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-24_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
720630HUVEC HRAS Target ID Apoptosis Mulitlpe Timepoints Caspase 3/7 Measured in Cell-Based System Using Plate Reader - 2156-30_Inhibitor_Dose_DryPowder_ActivityConfirmatorydepositor-specified cross reference
Description:
Primary Collaborators:
Brent Stockwell,Columbia University,614 Fairchild Center, MC 2406, 1212 Amsterdam Ave, New York, NY 10027,bs2198@columbia.edu,212-854-2948

Project Goal: The goal of the project is to interogate the biology related to mechanism of action for probes previously found to be synthetically lethal in cells expressing oncogenic Ras proteins and identify probe target related to mechanism of action.


Ras, apoptosis, cancer, VDAC, oxidative cell death, cytotoxicity, viability, ATP
Biological Relevance: The first rat sarcoma (RAS) oncogene was discovered as a genetic element
from the Harvey and Kirsten rat sarcoma viruses with the ability to immortalize mammalian cells1-3. Mutated
RAS oncogenes (i.e. HRAS, NRAS and KRAS) are found in 10-20% of all human cancers: KRAS mutations
are found in >90% of pancreatic cancers, 50% of colon cancers and 25% of lung adenocarcinomas; NRAS
mutations are found in 30% of liver cancers and 15% of melanomas, and HRAS mutations are found in 10% of
kidney and bladder cancers4.
RAS proteins are guanine-nucleotide-binding proteins with GTPase activity and are associated with the
plasma membrane. In the GTP-bound form, RAS proteins are mitogenic. Mutation of glycine-12 to other amino
acids (including valine, i.e. RASG12V) results in an oncogenic allele with constitutive mitogenic, transforming
activity and reduced GTPase activity5. Four downstream pathways activated by RAS proteins are (i) the
RAF/MEK/ERK pathway, which regulates cell-cycle progression, (ii) the PI3K/PDK/AKT pathway, which
regulates cell survival, (iii) the RalGDS pathway, which regulates membrane trafficking and vesicle formation,
and (iv) the PLCa/PKC pathway, which regulates Ca++ signaling.
We are searching for compounds and mechanisms that cause oncogene-selective lethality. Such
compounds eliminate tumor cells harboring specific oncogenic mutations, but have minimal effects on normal
cells lacking these mutations. In this project, we propose to screen for new compounds that are selectively
lethal to tumor cells expressing the RAS oncogenes. It is important to note that these compounds do not
directly inhibit RAS proteins or the RAS pathway, but rather cause cell death specifically in tumor cells
containing oncogenic RAS proteins.
Additional Information
Grant Number: R03 MH084117-01

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