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

## TL;DR

Direct-to-biology (D2B) is a new drug discovery method that skips purification steps, using crude reaction mixtures directly in biological tests to speed up and simplify the process.

## Contribution

The paper introduces D2B as a transformative approach in early drug discovery, emphasizing its integration with modern technologies like AI and high-content biology.

## Key findings

- D2B enables faster and more sustainable drug discovery by using nanoscale synthesis and direct screening.
- Commercial D2B services are now available, supporting ligand optimization and expanding the method's adoption.
- Challenges remain, including assay interference and technical limitations in miniaturization.

## Abstract

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.

Crude yet clever: Direct‐to‐biology workflows exploit nanoscale synthesis and plate‐based assays to accelerate hit discovery, save precious intermediates, and rethink early drug discovery.© 2026 WILEY‐VCH GmbH