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BioAssay: AID 624334

of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - Summary

The MKLP1/MgcRacGAP/Ect2 protein complex is well established as an essential regulator of cytokinesis. MKLP1 is a microtubule-driven molecular motor (kinesin), MgcRacGAP is a GTPase-activating protein for Rho family small G-proteins (RhoGAP), and Ect2 is a guanine nucleotide exchange factor for Rho proteins (RhoGEF). Interestingly, this complex also appears to contribute to human oncogenesis and more ..
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AID: 624334
Data Source: Southern Research Specialized Biocontainment Screening Center (MgcRacGap_Summary)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2012-06-25
Modify Date: 2013-03-25
Target
Depositor Specified Assays
AIDNameTypeComment
624300Discovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - HeLa CytotoxicityconfirmatoryCytotoxity Counter Screen
624330Discovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - Primary and Confirmatory ScreensconfirmatoryDiscovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - Primary and Confirmatory Screens
624351Discovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - Counter Screen Coupled EnzymeconfirmatoryDiscovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - Counter Screen Coupled Enzyme
624300Discovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - HeLa CytotoxicityconfirmatoryDiscovery of small molecule inhibitors of the oncogenic and cytokinetic protein MgcRacGAP - HeLa Cytotoxicity
652153Biochemical RhoGAP selectivity assay - MgcRacGAP inhibitionconfirmatoryBiochemical RhoGAP selectivity assay - MgcRacGAP inhibition
652148Biochemical RhoGAP selectivity assay - p50RhoGAPconfirmatoryBiochemical RhoGAP selectivity assay - p50RhoGAP
652149Biochemical RhoGAP selectivity assay - BCR GAPconfirmatoryBiochemical RhoGAP selectivity assay - BCR GAP
652142Biochemical MgcRacGAP assay detecting GTPase activation of the target GTPase Rac1 through the measurement of inorganic phosphate.otherBiochemical MgcRacGAP assay detecting GTPase activation of the target GTPase Rac1 through the measurement of inorganic phosphate.
Description:
Southern Research's Specialized Biocontainment Screening Center (SRSBSC)
Southern Research Institute (Birmingham, Alabama)
NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Assay Provider: Krister Wennerberg, FIMM & Southern Research Institute
Award: 1 R03 MH096578-01

Project Summary:
The MKLP1/MgcRacGAP/Ect2 protein complex is well established as an essential regulator of cytokinesis. MKLP1 is a microtubule-driven molecular motor (kinesin), MgcRacGAP is a GTPase-activating protein for Rho family small G-proteins (RhoGAP), and Ect2 is a guanine nucleotide exchange factor for Rho proteins (RhoGEF). Interestingly, this complex also appears to contribute to human oncogenesis and cancer malignancy. The proteins of the complex are overexpressed in many human cancers and the expression levels are directly correlated with a poor clinical prognosis. Therefore, development of small molecule inhibitors of this protein complex would be very valuable to further understand its biology of this protein and they may serve as leads for a novel class of anti-cancer drugs. Here we propose to utilize the assays and protocols we have established to identify and develop potent and selective inhibitors of MgcRacGAP with the support of one or more MLPCN centers. The development of publicly available small molecule inhibitors against the oncoprotein MgcRacGAP will prove valuable on several levels. First, basic researchers like our research group will be able to use these inhibitors to improve our understanding of MgcRacGAP and its role in carcinogenesis as well as normal biology. Second, these inhibitors may turn out to be used as starting points for the development of novel cancer drugs. Third, these experiments, if successful, can serve as a proof-of-principle for other proteins of the same type as MgcRacGAP but with different functions as potential drug targets.
Categorized Comment
BAO: version: 1.4b1090

BAO: bioassay specification: assay stage: confirmatory

BAO: bioassay specification: assay biosafety level: bsl1

BAO: assay format: biochemical format: protein format: single protein format

BAO: bioassay specification: assay measurement type: endpoint assay

BAO: bioassay specification: assay readout content: assay readout method: regular screening

BAO: bioassay specification: assay readout content: content readout type: single readout

BAO: meta target: molecular target: protein target: enzyme: protease

BAO: meta target detail: binding reporter specification: interaction: protein-small molecule

BAO: assay design: enzyme reporter: coupled enzyme: protease coupled enzyme

BAO: detection technology: fluorescence: fluorescence intensity

Additional Information
Grant Number: 1 R03 MH096578-01

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