MRK-952 Chemical probe for NUDT5

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 [1]. 

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.