As a test case for engaging the public into the drug design process, we selected the von Hippel Lindau E3-ligase (VHL). VHL is one of the commonly used E3-ligases for proteolysis targeting chimeras (PROTACs), a new drug modality which holds great promise for future medicines. VHL poses an excellent test case as example compounds that bind tightly to VHL exist as do many PROTACs derived from them . PROTACs are a rapidly growing segment of therapeutics . Their design is facilitated by their bi-functional nature, combining a targetspecific with an E3-ligase specific moiety. These two moieties are mostly independent, and a single E3-ligase moiety can be used with a range of protein-specific moieties to create PROTACs which degrade different target proteins . Currently, the chemical diversity of known VHL-ligands is limited, and most efforts concentrate on the usage of variations of groundbreaking findings by Crews and Ciulli . However, despite making good progress in de-peptidizing parts of the molecule to reduce polarity, the common hydroxyprolinol core crucial for binding affinity imparts unfavorable physicochemical properties due to its polar nature . Current molecules are thus limited in their potential use for clinically relevant oral PROTAC drugs due to their poor pharmacokinetic properties, particularly their high efflux as well as poor permeability and stability properties . Having this in mind, the objectives of the puzzle rounds were not only aimed at creating molecules with high affinity to VHL, but also directed by penalties or bonuses of different strength towards topological polar surface area (TPSA), hydrogen bond donor count, and cLogP. Here we describe the Drugit platform, the process we applied to funnel the diverse ideas from the players, the synthesis of selected molecules, and consecutive profiling.