A new platform from Promega enables scientists to measure compound binding directly in living cells, helping to translate biochemical hits into more reliable drug discovery decisions.
Promega Corporation has introduced a new platform designed to help drug discovery scientists study some of the most challenging protein targets in living cells, enabling earlier and more reliable validation of potential therapies.
The TarSeer™ BRETSA™ Target Engagement System, introduced at SLAS 2026 in Boston, is a live-cell assay technology that enables researchers to measure how well small molecules bind to target proteins inside intact cells. By providing early cellular insights into ligand-protein interactions, the system connects traditional biochemical assays with more complex cellular studies.
Many promising drug targets are difficult to interrogate using existing methods. Biochemical assays can identify potential hits, but these often fail to translate into meaningful activity in a cellular context. For targets that lack known probes or well-defined binding pockets, confirming whether a compound truly engages its intended protein can be particularly challenging.
Intractable therapeutic targets
According to Promega, the new platform is designed to address exactly this problem. Using a bioluminescence resonance energy transfer-based shift assay, known as BRETSA, the system detects changes in the thermal stability of proteins when they bind to a compound. This allows researchers to confirm target engagement directly in live cells, even for proteins that have previously been considered intractable.
You can now potentially study intracellular target engagement for any protein in live cells.
“You can now potentially study intracellular target engagement for any protein in live cells,” said Matt Robers, Associate Director of R&D at Promega. “This platform will give drug discovery researchers new starting points to go after a huge fraction of previously intractable therapeutic targets within the human proteome.”
Expanding access to difficult targets
Early validation of target engagement is a critical step in small-molecule drug discovery. Without reliable cellular assays, teams can struggle to prioritise compounds or understand why promising biochemical hits fail to progress.
The BRETSA system is intended to provide a more direct route to these answers. By measuring compound binding through changes in protein denaturation profiles, it offers a way to evaluate ligand potency and specificity inside living cells, rather than relying solely on purified proteins or indirect readouts.
Promega says this approach enables researchers to characterise weak or early chemical matter that might otherwise be overlooked. It can also be applied to targets that lack established assays, helping to broaden the range of proteins that can be pursued therapeutically.
Among the key advantages highlighted by the company are enhanced sensitivity, broad applicability across different target classes and a workflow that can be scaled from small follow-up studies to higher-throughput screening campaigns.
The platform uses an addition-only protocol compatible with both 96- and 384-well formats, making it suitable for integration into existing drug discovery pipelines.
Building on established technology
The TarSeer™ BRETSA™ system builds on Promega’s earlier NanoBRET® Target Engagement technology, which also uses bioluminescence resonance energy transfer to quantify protein-ligand interactions in cells. While NanoBRET requires specific probes for each target, BRETSA is designed to complement this approach by enabling studies of proteins that lack suitable probes or established assays.
By expanding this toolkit, Promega aims to support researchers working on a wider range of disease-relevant proteins, particularly those that have been difficult to address with conventional methods.
To introduce the technology to the scientific community, Robers presented data across multiple target classes during a podium session at SLAS 2026. The presentation, titled “BRETSA: An ultra-sensitive, broadly-applicable BRET method to measure target engagement through protein denaturation in live cells,” outlined the scientific principles behind the platform and demonstrated its application in real-world discovery workflows.
Promega staff were also available throughout the conference to discuss the system and its potential uses with researchers and industry partners.
A step toward more effective therapies
The ability to confirm target engagement early and directly in cells is increasingly seen as essential for improving the efficiency of drug discovery. By reducing uncertainty at the hit validation and lead optimisation stages, tools such as BRETSA could help teams focus resources on the most promising compounds and avoid costly late-stage failures.
Promega believes that expanding the range of proteins that can be studied in live cells will ultimately help researchers pursue new classes of therapeutic targets, including those involved in complex or poorly understood diseases.
