UCB9386

This probe is biochemically active and displays good levels of activity in a cellular nanoBRET assay. Given the many potentially functions of Nuak1 in evaluation or proposed in the literature, it is unclear what the cell activity would be across numerous cell lines. The compound does display good levels of kinase selectivity, however it is potent against both JAK2 and Nuak2 and it would be advised to have a second assay as part of the exploratory cascade to ensure that any desired effect is driven by the Nuak1 inhibition instead of JAK2 or Nuak2. Regarding its use as an in vivo tool compound, the Kp,uu is below the industry standard for brain penetration, which could impact the tool compounds' utility outside of the specific strain and gender mice in the original report. Furthermore, the kinase selectivity was conducted at 10 nM. It would be recommended to probe kinase inhibition at concentrations observed during dosing to better understand any pharmacological effects were indeed on target.