Adapting a Cell-Based Immunoassay for HTS: From the Bench to a 7,000-Compound Screen 

High-throughput screening (HTS) has been a central approach in small-molecule drug discovery since the late 1980s. It gives researchers a systematic way to find hits: compounds that act on a target and can be refined into drug candidates. The assays used in those screens matter, and cell-based assays are especially valuable because they bridge biochemical assays and in vivo models. Biochemical assays give direct readouts but miss the cellular context, while in vivo models are informative, but costly and slow. Cell-based assays enable scientists to study signaling pathways, target modulation and cytotoxicity in a more native environment, at a practical scale. 

image of puprle and blue antibodies coming together to form a luminescent compelx (lumit assay)

Many cell-based screens depend on engineered reporter systems: cells genetically modified so a pathway of interest produces a measurable signal, such as light or fluorescence. These cell lines take significant time and effort to build and maintain, and because they’re modified, they may not reflect disease-relevant cell states. As drug discovery moves toward primary cells and patient-derived lines, assays that detect endogenous proteins without genetic manipulation become more appealing. Those assays work across more cell types and are faster to set up. 

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Nitrile Gloves, Not Ribbons

Every October, the noise starts up again: it’s breast cancer’s turn for awareness. I brace for it a little every year. What bothers me isn’t the concept, it’s watching companies race to out-pink each other.

A pink ribbon on a shirt or a car can foster a certain amount of solidarity, but at the corporate level, the awareness noise is genuinely inescapable: a building lit up pink for the night, a pink yogurt lid, or a player running out onto the field in pink cleats. Many companies have run some version of the same campaign, and what actually happens to the profit from pink merchandise varies wildly: modest percentages, hard caps on total donations, or numbers that only recently moved after enough people asked questions.

In addition to the question of money is the question of effect: what does a company’s participation do? If the goal actually is awareness, I’ve never understood who remains unaware. It tends to generate goodwill instead, and the sometimes cynical among us might call that marketing, whether or not that’s the intent.

Here’s a sentence that’s true to me, one most people have their own version of: my sister had breast cancer. One in eight women in the U.S. will hear that diagnosis in her lifetime (though women aren’t the only ones who get it). So we are aware. We have been aware for a long time.

At one point, however, we actually needed awareness, in the literal sense of the word. When the American Cancer Society started its breast cancer awareness campaign in 1985, breast cancer was a disease people didn’t discuss in polite company, self-exams weren’t routine, and mammograms weren’t the norm they are now. Getting people to talk about it, check themselves, and get screened was a real, specific goal, and awareness did its job at the time. Last year marked the campaign’s fortieth anniversary, a point at which even the American Cancer Society’s own retrospective pointedly admitted: awareness alone isn’t enough anymore.

October runs on that word, awareness, as if noticing something were the same as solving it. As if on November 1st, we can dust off our hands, congratulate ourselves, and move on to the next color of the month. But breast cancer research doesn’t run on that calendar. Real, promising work has been happening. Learning about it might not change anything either, not directly, but it’s one step closer to what the American Cancer Society itself is now calling “Turning Awareness Into Action.”

More Than a Pretty Face

This starts, perhaps unexpectedly, with the axolotl, a foot-long Mexican salamander known for its perpetual smile and the feathery gills that fan out from its head like a spray of coral. The most common pet-store variety is also, conveniently for this piece, pale pink. It has become plastered across backpacks, folders, plush toys, and t-shirts. My nine-year-old niece and her friends are obsessed with them.

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ADC Development: The Questions Running in the Background

You’ve had food stuck in your teeth at some point during a conversation you thought was going well. Or toilet paper trailing from the back of your shoe on a day you felt particularly put together. Maybe you’ve even forgotten to color in your very blonde eyebrows and spent the rest of the day looking like someone erased the top half of your face. But you had no idea. You’re walking around with the quiet, complete confidence of someone operating on incomplete information.

You weren’t wrong about anything you could see. You just couldn’t see everything, which is a different problem than getting a bad result. A bad result tells you something is wrong, but this doesn’t. This happens in the lab too. The number is clean, the program is advancing, and somewhere in the data, something is happening that your readout has no way to show you.

Antibody-drug conjugate (ADC) development has a version of this problem. The cytotoxicity readout is real, reliable, and correct. It’s also an aggregate, and an aggregate compresses everything that happened into a single number. That number can’t tell you which mechanisms produced it, which ones are underperforming, or what to change if the program stops working. It just tells you cells died, or they didn’t. You’re walking around with the quiet, complete confidence of someone operating on incomplete information.

Cytotoxicity: Where Every Program Begins

Cell viability assays were built to answer one question: did the cells die? Increase the dose, more cells die. Decrease it, fewer do. The curve is clean, the data is reliable, and the payload is doing what it was designed to do. For cytotoxicity, it’s the right question to ask.

That question has an established platform with consistent, reproducible data: our CellTiter-Glo® and RealTime-Glo™ Assays.

For most ADC programs, this is where the measurement work starts and stops, but it should only be where it starts. The question they answer well is only one of several your ADC is raising. The number means what it says, but the question it answers has a boundary, and the boundary leaves you with an incomplete picture.

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The Calcium-Platelet Connection in Cancer Metastasis 

Most cancer-related deaths from solid tumors aren’t caused by the primary tumor itself, but are the result of metastasis. Metastasis is the process by which cancer cells break away from the primary tumor, travel through the bloodstream and establish new tumors in distant tissues. This is a complex, multi-step process and cancer researchers have spent decades trying to understand and disrupt the metastatic cascade. What is known: platelets and calcium play important roles in metastasis. What is unknown: How do these two factors interact?  

Here, we explore a recent study published in Scientific Reports by researchers at George Washington University1. They investigate how calcium levels influence platelet-cancer cell interactions and what happens when both factors converge.  

red blood cells,activated platelet and white blood cells microscopic photos
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Advancing Canine Cancer Immunotherapy through One Health Comparative Oncology Research

The Case for Canine Immunotherapy

Cancer does not respect species boundaries. Each year more than four million dogs are diagnosed with cancer (1), making it the leading disease related cause of death in the canine population. Osteosarcoma, lymphoma, mast cell tumors and mammary carcinomas are among the most prevalent (1). In many cases, these tumors in dogs bear striking biological and molecular similarities to their human counterparts.

This convergence is the foundation of the Comparative Oncology (2) framework and One Health Initiatives. Companion pets, like dogs and cats, share our environments, our lifestyles and increasingly our therapeutic challenges. When research advances in veterinary oncology, it can open windows into human disease as well.

Comparative oncology integrates the advances and research of veterinary science. Dog and cat against a background of antibodies.
Comparative oncology integrates the advances and research of veterinary science, especially those of companion animals like dogs and cats, into more general oncology research, advancing the entire field of oncology.

What Veterinary Checkpoint Immunotherapy Brings to Comparative Oncology

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Screening Disease-Relevant Biology: How the Endo-GeneScreen Platform Uses Endogenous Protein Detection to Drive Drug Discovery 

Drug discovery has long grappled with a fundamental tension in high-throughput screening: the more biologically relevant your model, the harder it is to scale. Phenotypic assays in primary disease-relevant cells offer rich biological context, but capturing meaningful, target-specific readouts from these complex systems at screening scale has remained a significant challenge.  In contrast, simpler, more scalable systems are easier to deploy but sacrifice the biological fidelity that makes hits meaningful. A recent study by Samowitz et al. in Nature Communications describes an interesting approach to resolve this tension, the Endo-GeneScreen (EGS) platform. A high-throughput screening system designed to enable scalable detection of endogenous protein levels within disease-modeling cellular contexts. 

A Well-Chosen Proof of Concept 

The authors selected Syngap1 as their proof-of-concept target to develop and demonstrate this approach. De novo mutations in this gene that lead to haploinsufficiency are among the most common genetic causes of sporadic neurodevelopmental disorders, including intellectual disability, autism, and epilepsy. Small molecules that boost SynGAP protein levels back toward wildtype would address the root cause of these disorders rather than managing downstream symptoms. Importantly, Syngap1 function is closely tied to cortical excitatory neurons. Well-validated in vitro and in vivo models for these neurons already exist, creating an integrated system for both discovering new compounds and validating them in the same biological context. That continuity is an important step toward improving the translational relevance of lead molecules coming out of the screen. 

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Trends and Tools Transforming Drug Discovery: Five Takeaways from Discover Glo 2025

In biologics, cell therapy, and targeted protein degradation, the science is moving fast—and so are the tools. From GPCR-targeted therapies to real-time CAR-T manufacturing tools, new techniques are reshaping how scientists approach drug development, live-cell imaging, and protein degradation.

The “Bringing Light to Science” Discover Glo 2025 speaker series brought together researchers from across academia and industry to share real-world examples of how bioluminescent technologies are helping them advance their research. Now available on demand, these sessions offer fresh perspectives and actionable takeaways on the future of therapeutic development, cellular analysis and assay design.

We’ve distilled five key takeaways from the sessions—practical insights you can apply to your own work or use to stay current with where the field is heading.

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Promega Fc Effector Assays: Measure Every Mechanism

This post is written by Kai Hillman, PhD, Promega Corporation.

Every day, scientists push the boundaries of what’s possible with monoclonal antibodies (mAbs)—from targeting cancer cells to calming autoimmune-driven inflammation. These therapies rely not only on binding but on engineering the desired immune response. The suite of Promega Fc Effector Assays helps you understand these interactions from receptor binding and function, through bridging studies. With consistency, sensitivity, and scalability, these assays support teams from early discovery through lot release.

This article draws on real-world publications and product insights to show how Promega assays are powering next-generation immunotherapies—and redefining how we measure immune engagement.

Schematic diagramming the suite of Promega Fc effector assays in one seamless workflow to support antibody development across the pipeline.
Figure 1. Promega delivers the most comprehensive suite of Fc effector assays in one seamless workflow to support antibody development across the pipeline.
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Cellular Selectivity Profiling: Unveiling Novel Interactions and More Accurate Compound Specificity

This blog was written by guest contributor Tian Yang, Associate Product Manager, Promega, in collaboration with Kristin Huwiler, Manager, Small Molecule Drug Discovery, Promega.

Determining the selectivity of a compound is critical during chemical probe or drug development. In the case of chemical probes, having a clearly defined mechanism of action and specific on-target activity are needed for a chemical probe to be useful in delineating the function of a biological target of interest in cells. Similarly, optimizing a drug candidate for on-target potency and reducing off-target interactions is important in the drug development process (1,2). A thorough understanding of the selectivity profile of a drug can facilitate drug repurposing, by enabling approved therapeutics to be applied to new indications (3). Interestingly, small molecule drugs do not necessarily require the same selectivity as a chemical probe, since some drugs may benefit from polypharmacology to achieve their desired clinical outcome.

Selectivity profiling panels based on biochemical methods have commonly been used to assess compound specificity for established target classes in drug discovery and chemical probe development. Biochemical assays are target-specific and often quantitative, enabling direct measurements of compound affinities for targets of interest and facilitate comparison of compound engagement to a panel of targets. As an example, several providers offer kinase selectivity profiling services using different assay formats and kinase panels comprised of 100 to 400 kinases (4). However, just as biochemical target engagement does not always translate to cellular activity, selectivity profiles based on biochemical platforms may not reflect compound selectivity in live cells (5).

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Targeting Epigenetic Regulators in Cancer: The Promise of BET and HDAC Inhibitors

This blog was written in collaboration with Tian Yang, Associate Product Manager at Promega.

Cancer is often driven not only by genetic mutations, but by changes in how genes are turned on or off—epigenetic alterations. Two key players in this space are bromodomain and extra-terminal (BET) proteins and histone deacetylases (HDACs).

BET proteins help activate gene expression by recognizing acetylated lysines on histones, while HDACs remove these acetyl groups, repressing transcription. When these mechanisms become dysregulated, they can promote tumor growth or silence tumor suppressors.

To counteract this dysregulation, researchers have developed inhibitors that target BET proteins and HDACs. While combinations of these drugs have shown synergy, using two separate compounds introduces challenges with dosing, toxicity and pharmacokinetics. Recent efforts have focused on designing multitarget inhibitors—single molecules that can simultaneously block BET and HDAC activity.

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