Direct‐to‐Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery

Direct-to-biology (D2B) has emerged as a transformative concept in early drug discovery, defined by the direct on-target screening of crude reaction mixtures without prior purification. First coined in 2021, the approach builds on advances in nanoscale synthesis platforms and was shaped by seminal studies that demonstrated the feasibility of plate-based microscale chemistry for library generation. Today, D2B is increasingly adopted in academia and industry, with campaigns exploring diverse reaction classes, targeting modalities, and assay platforms. Thus, very recently, the first commercial providers now offer D2B services for ligand optimization, further driving adoption. Yet, despite clear advantages in speed, cost, and sustainability, D2B also faces limitations from assay interference and technical constraints in reaction miniaturization. Looking ahead, integration with AI-driven design and high-content biology promises to expand the scope of D2B and position it as a robust complement to traditional discovery paradigms.