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
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.
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
Data Table (Concise)