Bifunctional molecules and in particular Proteolysis Targeting Chimeras (PROTACs) have an increasing clinical presence with the first examples directed towards indications beyond oncology emerging in 2024. The Farnaby Group, located at the University of Dundee Centre for Targeted Protein Degradation, is focussed on using a variety of induced proximity strategies to discover chemical probes for Central Nervous System disease therapeutic concepts, including identifying CNS active bifunctionals/PROTACs. The conventional discovery of PROTACs is generally reliant on the time consuming and expensive linear synthesis of 100s to 1000s of molecules with no clear design guidelines on how this can be conducted in a manner that may lead to CNS activity. Here, we developed a novel direct-to-biology (D2B) platform that incorporates multiple types of conjugation chemistries within a 1-well-2-step protocol with sufficient conversion for direct cellular testing. We exemplify our approach by demonstrating how we can move quickly from no previous structure activity data to potent and selective target protein degraders, suitable for investigation of downstream signalling pathways to interrogate therapeutic hypotheses, and for in vivo profiling in the CNS without any requirement for optimisation beyond the compounds discovered direct from the initial screen.