I think >1 μM activity can be ok depending on what kind of target and what kind of IC50 assay is done. Of course, as you know, comparing IC50s is famously somet

I think >1 μM activity can be ok depending on what kind of target and what kind of IC50 assay is done. Of course, as you know, comparing IC50s is famously something that cannot/should not be done, because they are assay and condition dependent, even for the same target, which is another reason why a μM cutoff is not set in stone for me. A value like that can be OK when trying to find a (clean, well behaved, synthesizable) early hit for later optimization into an actually useful probe or drug. However, in this case the IC50 are high double digits so I agree you will never get these kind of concentrations in humans without causing problems due to off-target activity.