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BioAssay: AID 1661

Summary of the absorbance assay for the identification of compounds that inhibit VHR1.

Assay Provider: Dr. Lutz Tautz, Sanford-Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA) ..more
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Probe(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Probe(1)
 
 
Active(1)
 
 
AID: 1661
Data Source: Burnham Center for Chemical Genomics (BCCG-A183-VHR1-Absorbance-Summary-Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-04-06
Modify Date: 2010-12-30

Data Table ( Complete ):           Active    All
Target
BioActive Compound: Chemical Probe: 1    Active: 1
Depositor Specified Assays
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AIDNameTypeComment
1654uHTS absorbance assay for the identification of compounds that inhibit VHR1.confirmatoryuHTS absorbance assay for the identification of compounds that inhibit VHR1
1878Fluorescent assay for identification of compounds that inhibit VHR1confirmatoryFluorescent assay for identification of compounds that inhibit VHR1
1957SAR VHR1 Fluorescent Assay for In Vitro dose response studiesconfirmatorySAR VHR1 Fluorescent Assay for In Vitro dose response studies
1958SAR VHR1 absorbance Assay for In Vitro dose response studies.confirmatorySAR VHR1 absorbance Assay for In Vitro dose response studies
1992HTS Colorimetric assay for the identification of compounds that inhibit VHR1screeningHTS Colorimetric assay for the identification of compounds that inhibit VHR1
2004SAR Colorimetric assay for the identification of compounds that inhibit VHR1confirmatorySAR Colorimetric assay for the identification of compounds that inhibit VHR1
2074SAR Fluorescence Assay for VHR1 Inhibitors using DiFMUPconfirmatorySAR Fluorescence Assay for VHR Inhibitors using DiFMUP
2082SAR Fluorescence HePTP Assay for Selectivity Study of VHR1 Inhibitors using DiFMUPconfirmatoryHePTP assay as counterscreen assay
2083SAR Fluorescence MKP-1 Assay for Selectivity Study of VHR1 Inhibitors using DiFMUPconfirmatoryMKP-1 assay as counterscreen assay
2678SAR analysis of chemical inhibitors of HePTP using a Fluorescent assay - Set 2confirmatory
2679SAR analysis of inhibitors of MKP-3 - Set 2confirmatory
2684SAR VHR1 Fluorescent Assay for In Vitro dose response studies Set 2confirmatory
449733SAR analysis of compounds that inhibit VHR1, Fluorescent Assay - Set 2confirmatory
1055In Vitro MKP-3 Dose Response Assay for SAR Studyconfirmatory
2070MOA VHR1 Fluorescent secondary assay for identification of redox-state modulating compoundsconfirmatory
488861Dose Response Confirmation of compounds that inhibit VHR1 in Fluorescent Assayconfirmatory
488923Dose Response confirmation of compounds that inhibit HePTPconfirmatory
540288SAR VHR1 Fluorescent Assay for In Vitro dose response studies Set 3confirmatory
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1 R03 MH084230-01A1
Assay Provider: Dr. Lutz Tautz, Sanford-Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)

Protein tyrosine phosphatases (PTPs) play vital roles in numerous cellular processes and are implicated in a growing number of human diseases, ranging from cancer to cardiovascular, immunological, infectious, neurological, and metabolic diseases. The Vaccinia H1-related (VHR) PTP is a dual-specific Erk and Jnk phosphatase, the loss of which causes specific cell cycle arrest in HeLa carcinoma cells, suggesting that VHR inhibition may be a useful approach to halt the growth of cancer cells without detrimental effects on normal cells. Recent studies by collaborators and us suggest that VHR is upregulated in several cervix cancer cell lines, in squamous intraepithelial lesions, and squamous cell carcinomas of the uterine cervix.

This summary AiD reports the identification of a VHR-selective inhibitor as a probe molecule, SID 85256223(ML113). From primary HTS (AID 1992) and subsequent hit confirmation using dose-response assay (AID 2004), some VHR inhibition hits were confirmed. SAR studies were performed on a series of molecules (AID 2074). Top hits from the SAR studies (AID 2074) were further studied in two selective assays (AID 2082 and AID 2083) to further access their selectivity toward VHR. Those efforts resulted in the identification of a novel, potent and selective probe molecule of SID 85256223. Work on the development of this probe has been published (J. Med. Chem., 2009, 52 (21), pp 6716-6723)
Protocol
Please see pertinent AID: 1654, 1878, 1957, 1958, 1992, 2004, 2074, 2082, 2083, 2678, 2679, 2684, 449733
Comment
This AID is used to summarize the results of this MLPCN project. Probe molecules are defined as the positives of this assay and assigned a score of 100
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Assay 1: (qualifier)This qualifier is to be used with the next TID, IC50. If the qualifier is "=", the IC50 result equals the value in that column; if the qualifier is ">", the IC50 result is greater than that valueString
2Assay 1: SAR Fluorescence assay for VHR (AID 2074) (IC50)FloatμM
3Assay 2: (qualifier)String
4Assay 2: HePTP assay as counterscreen assay (AID 2082) (IC50)FloatμM
5Assay 3: (qualifier)String
6Assay 3: MKP-1 assay as counterscreen assay (AID 2083) (IC50)FloatμM
7ML#ML# for the compoundString
Additional Information
Grant Number: 1 R03 MH084230-01A1

Data Table (Concise)
Classification
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