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BioAssay: AID 2114

qHTS Assay for Inhibitors of Human Galactokinase (GALK): Summary

Assay Submitter (PI): Kent Lai (University of Utah School of Medicine, 50 N Mario Capecchi Drive, Salt Lake City, UT 84132) ..more
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 Tested Compounds
 Tested Compounds
All(14)
 
 
Probe(1)
 
 
Active(12)
 
 
Inactive(2)
 
 
 Tested Substances
 Tested Substances
All(14)
 
 
Probe(1)
 
 
Active(12)
 
 
Inactive(2)
 
 
AID: 2114
Data Source: NCGC (GALK538)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2009-11-06
Modify Date: 2011-03-08

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: galactokinase 1 [Homo sapiens]
Description ..   
Protein Family: Galactokinase galactose-binding signature

Gene:GALK1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: Chemical Probe: 1    Active: 12
Related Experiments
Show more
AIDNameTypeComment
1868qHTS Assay for Inhibitors of Human Galactokinase (GALK)Confirmatorydepositor-specified cross reference: GALK inhibition primary assay (Kinase-Glo)
2015Confirmation Assay for Inhibitors of Human Galactokinase (GALK)Confirmatorydepositor-specified cross reference: GALK inhibition confirmation assay (Kinase-Glo)
2035Confirmatory Assay for Inhibitors of Human Galactokinase (GALK): Phenol-HRP redox assay counterscreenConfirmatorydepositor-specified cross reference: GALK inhibition secondary assay: Redox activity counterscreen
2499Confirmation Assay for Inhibitors of Human Galactokinase (GALK): probe SARConfirmatorydepositor-specified cross reference: GALK inhibition confirmation assay for probe SAR (Kinase-Glo)
2502Confirmatory Assay for Inhibitors of Human Galactokinase (GALK): Phenol-HRP redox assay counterscreen for probe SARConfirmatorydepositor-specified cross reference: GALK inhibition secondary assay: Redox activity counterscreen for probe SAR
2506Confirmatory Assay for Inhibitors of Human Galactokinase (GALK): CDP-Me assay counterscreen for probe SARConfirmatorydepositor-specified cross reference: GALK inhibition secondary assay: CMK counterscreen for probe SAR
2547Secondary Assay for Inhibitors of Human Galactokinase (GALK): HEK-293 Cell Viability AssayConfirmatorydepositor-specified cross reference: GALK inhibition secondary assay: cytotoxicity assay for probe SAR
493188Confirmation Assay for Inhibitors of Human Galactokinase (GALK): SAR round 2Confirmatorydepositor-specified cross reference
493189qHTS Validation Assay for Inhibitors of Human Galactokinase (GALK)Confirmatorydepositor-specified cross reference
720664On Hold
743373On Hold
743401On Hold
Description:
NIH Molecular Libraries Probe Production Centers Network [MLPCN]
NIH Chemical Genomics Center [NCGC]
MLPCN Grant: R03 MH085689-01
Assay Submitter (PI): Kent Lai (University of Utah School of Medicine, 50 N Mario Capecchi Drive, Salt Lake City, UT 84132)


Inherited deficiency of galactose-1-phosphate uridyltransferase (GALT) can result in a potentially lethal disorder called Classic Galactosemia (OMIM 230400). Several lines of evidence indicate that an elevated level of galactose-1-phosphate (gal-1-p), the product of galactokinase (GALK), is a major, if not sole, pathogenic mechanism in patients with classic galactosemia. Therefore, finding inhibitors of GALK is a potential novel therapy for this inherent metabolic disease and is the long term goal of this project.
GALK (provided by Dr. Kent Lai (University of Utah School of Medicine) was assayed using Kinase-Glo Plus (Promega; PubChem AID: 1868) and putative actives were first confirmed in the same assay (PubChem AID: 2015). To determine the validity and selectivity of active compounds against GALK a counterscreen targeting the structurally related GHMP kinase CMK was used (PubChem AID 2017). Further, as the primary assay contained the reducing reagent DTT, compounds were evaluated and flagged for redox-depedent activity using a colorimetric assay (PubChem AID: 2035).

A probe compound (SID 87550830; probe number ML152) was identified with IC50 = 1.0 uM to galactokinase.
Protocol
Please refer to other AIDs (1868, 2015, 2017, 2035) for detailed assay protocols.
Comment
This summary is written for the purposes of summarizing the probe activities from the project. MLPCN probes are given a score of 100. Molecules in the prior art are given a score of 80. Other, less active molecules are given a score of 50. Molecules pending validation are given a score of 10. Inactive compounds are given a score of 0.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML152
PubChem Substance ID (SID) for probe 1: 87550830
PubChem Compound ID (CID) for probe 1: 664331
IC50/EC50 (nM) for probe 1: 1000
Target for probe 1: GALK (gi: 4503895)
Disease relevance for probe 1: Rare Disease
Anti-target for probe 1: CDP-Me
Fold selectivity for probe 1: >10
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK56237/ (ID: 2510050)
Grant number for probe 1: MH085689-01
NCBI Book chapter title for probe 1: Toward Improved Therapy for Classic Galactosemia
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1Phenotype GALKIndicates type of activity observed based on the compound activity in GALK confirmation assay.String
2Potency_GALKThe concentration of sample yielding half-maximal inhibition in GALK confirmation assay.FloatμM
3Potency_CDP-Me The concentration of sample yielding half-maximal inhibition in CDP-Me counter assay.String
4Potency_RedoxThe concentration of sample yielding half-maximal inhibition in Redox counter assay.String
Additional Information
Grant Number: R03 MH085689-01

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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