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MSD in collaboration with the SGC has developed a chemical probe MRK-952 for NUDT5. This chemotype complements that of TH5427 as reported by Helleday et al .
MRK-952 inhibits NUDT5 with IC50 = 85 nM in an AMP-Glo assay with the substrate ADP-ribose. To study the cellular on-target engagement an energy transfer probe (NU074573a) was developed. In the nanoBRET assay MRK-952 inhibited NUDT5 with EC50 = 23.5 ± 4 nM. MRK-952-NC is a closely related negative control with IC50 = 10 micromolar.