Screening for novel inhibitors of Glutathione Peroxidase 1 and 4

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

The collaborative team aims to identify novel small molecule inhibitors of GPx1 and GPx4 that have potential as anticancer therapeutics. As this is a dual effort between KI and NCATS, the graduate student spent time at KI producing and purifying active selenocysteine-containing recombinant human GPx1 and GPx4 using a novel method developed in the KI lab. Upon return to NCATS, multiple assay formats were assessed for suitability in 1536-well format, and a glutathione reductase (GR) coupled assay using quantification of NADPH as the readout was selected. As of now, a GPx1 assay has been optimized and miniaturized for 1536-well format, and several annotated libraries have been screened. Development and optimization of the GR-coupled GPx4 assay is ongoing. Hits will be counter-screened against a GR assay that has also been developed and optimized.