Fundamentally, drugs work by interacting with host proteins to modify their activity and achieve therapeutic effect. Our target identification services leverage discovery proteomics to directly quantify thousands of proteins per sample, including those now accessible via emerging drug modalities, alongside AI-based validation to find protein targets that are:
We provide quantitative protein measures, including quantification of protein copy numbers, to identify proteins that are uniquely expressed or over-expressed in diseased tissue compared to both normal adjacent tissue as well as a panel of other normal human tissues.
We apply AI to assess therapeutic tractability – whether the protein structure can be bound or otherwise accessed by the drug (e.g., by proximity-induced degradation) – to better predict drug efficacy and potential off-target effects.
From ADCs to radioligand pharmaceuticals to targeted protein degraders, innovative drug modalities have increased the number of tractable targets from a few hundred to several thousand proteins. Our services provide rapid, comprehensive characterization of this expanded breadth of potential targets, including on the tumor surface, to identify the best target for your therapy.
Much work in target identification to date has relied upon human genetics and RNA sequencing to identify differentially expressed genes. Ultimately, however, druggability occurs at the protein level. DNA and RNA measures are limited surrogates for quantitative protein levels, and are often not well correlated in disease or treated states.
Using mass spectrometry, Sapient’s methods directly measure thousands of proteins and post-translational modifications (PTMs) in cells and tissue. We provide quantitative data on differentially expressed proteins, including those on the cell surface, to generate disease protein libraries across therapeutic areas – including oncology, neurology, and immunology – that may represent viable targets. Our approaches include:
The majority of drug target proteins. Proteomics-based target identification uses mass spectrometry to directly measure thousands of proteins in disease-relevant tissues or biofluids – rather than relying on indirect RNA or genetic proxies – to discover proteins that are differentially expressed, disease-modifying, and therapeutically tractable.
RNA ≠ protein. DNA and RNA are limited surrogates for quantitative protein levels and are often poorly correlated with actual protein expression in disease or treated states. Mass spectrometry-based proteomics provides direct, quantitative measurement of proteins and post-translational modifications (PTMs), capturing the functional biology that ultimately determines druggability.
Sapient’s target identification workflows are compatible with fresh-frozen tissue, FFPE tissue, cells, plasma, and other biofluids. Importantly, FFPE compatibility unlocks vast archives of clinically annotated tumor samples for retrospective target discovery.
Beyond differential expression, we apply deep biocomputational analysis to contextualize targets within biological and signaling pathways, confirming whether they are mechanistically involved in disease. We then use AI to assess therapeutic tractability – whether the protein structure can be bound or accessed by a given drug modality – to predict efficacy and potential off-target effects.
Once a robust target has been identified, Sapient can then develop a targeted, quantitative protein assay with absolute quantification for translation to clinical applications.
