Category: Assay Development and Screening
NFS1 is a cysteine desulphurase required for the assembly of iron-sulphur clusters (FeS) and intracellular iron homeostasis. FeS are essential prosthetic groups involved in catalysis, protein folding/stability, and sulphur donating enzymes.
Several critical pathways in cancer cells are dependent on intact FeS cluster assembly including haem biosynthesis, energy production, DNA replication and repair, ribosomal recycling and fatty-acid biosynthesis.
NFS1 RNAi leads to loss of activity of several key iron-sulphur enzymes, morphological changes of mitochondria and growth inhibition of cultured tumour cells.
Current NFS1 assays (including ELISA; methylene blue; circular dichroism; alanine or 55Fe or sulphur quantification) are not suited to support Drug Discovery.
Here we present the development of a robust fluorescent NFS1 assay suitable for HTS.
Paul Hales– Sr. Scientist I, Takeda Pharmaceuticals Inc, Cambridge, MA