In this study, we present a novel library synthesis and screening approach, that was able to identify an in vivo active bifunctional degrader of chemical probe quality directly from the initial screen. We started by establishing use of linker reagents that can be selectively conjugated in high conversion, with two different reaction types at either end, so-called orthogonally reactive linkers. Specifically, we used a combination of SN2 and CuAAC reactions, choosing these reaction types due to their potential for high conversion, whilst limiting the extra polar surface area and hydrogen bond donor contribution.