Macrocyclic DNA-encoded libraries (DELs) offer a powerful approach for discovering novel therapeutics, especially against challenging biological targets. Previously, we identified potent, selective macrocyclic inhibitors of Bcl-2 family proteins, optimized to low-nanomolar potency with favorable drug-like properties. Building on this success, our next-generation macrocyclic DEL features diverse ring sizes, rich stereochemistry, and proprietary chemistries, enabling efficient exploration of complex targets and accelerating the path to high-quality leads.