Yoctoreactor technology (yR) is employed to generate DNA-encoded small molecule libraries of maximum fidelity for seamless drug discovery. Through efficient self-assembly of DNA oligonucleotides, 3D DNA structures are formed ? each is serving as a small chemical reactor. Building blocks covalently linked to the DNA oligonucleotides are thus pre-organized in the center of a DNA junction, and chemical reactions can take place efficiently due to the proximity effect. The DNA acts both 1) as a structural director for the chemical reactions and 2) as a distinct barcode from which each library member may be identified by DNA sequencing. All this is possible in a single-tube format due to a tight correspondence between DNA codes and the molecules synthesized. Herein we describe the assembly and analysis of a multi-million membered small molecule library that was prepared using the yR technology - including a comparison to various standards for drug-likeness. Furthermore, the yR library was interrogated using proprietary Binder Trap Enrichment technology (BTE) which is a homogeneous screening method. This method employs a unique principle of trapping small molecule binders together with the protein target in miniscule droplets and enables direct identification of potent inhibitors directly from the library. Case stories will be presented, including interleukin 6 receptor (IL-6R) ? a clinically validated protein ? protein interaction target which is implicated in cancer and multiple inflammatory and autoimmune diseases. Potent inhibitors were also identified for traditional target, e.g. p38-alpha kinase. In both examples, nanomolar inhibitors were identified directly from the library without hit maturation.