Primary Screening for Target engagement in drug discovery

Select hits that bind in cells from day one

Primary screening identifies starting points for new therapeutic programs that can be developed into compounds showing meaningful activity in biologically relevant contexts. Compound libraries are screened using biochemical or cell-based methods against defined targets, with early hits supporting subsequent optimization and development.

Decisions around biological relevance, assay technology, throughput, and library selection are addressed early, as these factors directly influence screening efficiency, reproducibility, and hit quality. Assays are optimized and validated with clear performance criteria to ensure robustness across screening campaigns. For high-throughput screening, practical considerations such as automation, liquid handling, and assay controls are incorporated from the outset. Data analysis strategies are defined to identify true hits while controlling false positives and minimizing bias. Pilot screens assess signal window, Z′-factor, and assay variability before full-scale screening.

Screen smarter with Targeted Profiling

Primary screening with CETSA measures target engagement directly in cells, capturing therapeutically relevant context such as compound permeability, target abundance, localization, and cellular cofactors. This engagement-first approach strengthens hit selection, reduces false positives, and ensures compounds entering optimization are supported by mechanistically meaningful cellular evidence.

Primary Screening is enabled by our Targeted Profiling Service

Targeted Profiling

Validate mechanistic hypotheses and confirm that on-target engagement occurs in the intended cellular context.

Learn more

A Case Study in CDK4 Hit Identification

Discover how CETSA® technology can be applied to identify novel chemotypes and strengthen early drug discovery decisions — even for known targets like CDK4.

Learn more

Employing CETSA in Primary Screening for p53 Binders

Targeting p53, a key tumor suppressor protein often labeled “undruggable,” poses a major challenge in oncology research. Yet, overcoming this challenge could unlock transformative cancer treatments

Learn more