IMP-1710

This looks like a potent and selective inhibitor of UCHL1. There are still few things to keep in mind when using this compound: 1)The unbiased quantitative chemical proteomic profiling was conducted at a maximum concentration of 200nM. It is thus not impossible that the drug shows covalent off-target effects when going to 1uM, the upper limit of the suggested concentration range. 2) Perhaps more importantly, the compound has not been profiled for any none covalent off-target effects or covalent effects that cannot be captured by these particular proteomics methods. For example, the compound features a typical kinase binding motif and it would be reassuring to see kinase or broader receptor screening though I appreciate that would be expensive.  

IMP-1711 (compound 3) is a well-characterized reversible covalent inhibitor of UCHL1 with excellent selectivity and high potency. The probe compound has demonstrated robust cellular target engagement at sub-micromolar concentrations. Moreover, a structurally similar compound (R)-enantiomer of the parent compound shows no inhibition (>100 uM) towards UCHL1 which may be useful in target validation studies.

I would recommend 100-200 nM for target engagement or proteomics analysis. Investigation of downstream effects in models such as IPF may need up to 1000 nM of this compound.