JNJ-9350

10 µM is >10-fold higher than the enzymatic IC50 for the related counter-target PAOx. In addition, the off-target profiling suggests that other activities may be present at 10 µM. The user should consider these two findings when interpreting experiments performed at the upper end of the suggested concentration range.

The compound offers a useful SMOX tool and as such contributes to the understanding of this target biology. The presence of an inactive and closely related analogue helps offset concerns around off-target effects. Of note, the tool does have a reasonably significant drop-off in potency between enzyme and cell assays of around 1 orders of magnitude. An order of magnitude fall-off is more typical and suggests either efflux liabilities (which may be unlikely, given reasonable oral bioavailability) or other permeability issues, or high non-specific binding to cellular or serum proteins. The molecular architecture is relatively simple and may suggest some concerns around interactions with other off-target proteins. An awareness of this is important in deconvoluting observed pharmacology and wider profiling against counter targets may be advisable in appropriate circumstances.