Cellular Selectivity Profiling: Unveiling Novel Interactions and More Accurate Compound Specificity

Posted on by Promega

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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Is Your Lab Environment Messing with Your Results? How to Spot the Signs Early

Posted on by Promega

This blog was contributed by guest Avi Aggarwal, 2025 summer intern at Promega.

If you’ve ever scratched your head over inconsistent experimental results, especially ones that seem to fluctuate for no obvious reason—you’re not alone. Sometimes the problem isn’t your pipetting, your reagents, or even your protocol. It might be the room itself.

Changes in temperature, humidity, or even invisible dust particles can quietly throw off your results. Something as simple as moving your thermocycler under an air vent or setting up a plate reader where sunlight hits it in the afternoon could cause subtle but significant issues.

Scientist removes samples from liquid nitrogen tank, affecting the immediate laboratory environment.
Any number of things can affect the laboratory environment, from opening a cryo tank to moving an instrument under an air vent.

Our Project to Learn How Subtle Environmental Changes Can Affect Sensitive Lab Equipment

We spent some time developing an environmental anomaly detection framework aimed at helping scientists understand how subtle environmental changes can affect sensitive lab equipment and experimental results. Our team set out to monitor real-world lab conditions using temperature and humidity sensors, including live testing with a GloMax® Discover platform and Sensirion SHT45 sensors. We also worked with open-source environmental datasets to simulate a variety of lab-like conditions, such as daily cycles, sudden temperature spikes, and slow humidity drifts.

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Developing an Experimental Model System to Understand the Tumor Microenvironment of Melanoma Brain Metastases

Posted on by Michele Arduengo, PhD

Cancer’s greatest threat is its ability to spread to other tissues—a process known as metastasis. Melanoma, a form of skin cancer, exemplifies this devastating progression. Although treatable when caught early—with surgical removal resulting in over 99% survival at five years—once melanoma metastasizes, five-year survival rates plummet dramatically to around 27%. Even more concerning, melanoma exhibits a particularly high tendency to invade the central nervous system, causing melanoma brain metastases (MBMs) that are incurable and reduce median survival to just 13 months.

To understand metastasis, we need reliable and realistic experimental models. Traditional cell cultures on plastic dishes are limited, failing to replicate the intricate spatial organization and biochemical interactions within living tissues. Animal models are informative but expensive, ethically complex, and not always accurate for human diseases. Addressing this critical gap, Reed-McBain and colleagues (2025) introduced an innovative microphysiological system (MPS) designed to simulate the tumor microenvironment in the brain affected by metastatic melanoma.

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Unlocking the Power of Live-Cell Kinetics in Degrader Development

Posted on by Kelly Grooms

In targeted protein degradation (TPD), timing is everything. Understanding not just whether a degrader works—but how fast, how thoroughly and how sustainably—can dramatically influence early discovery decisions. Dr. Kristin Riching (Promega) dove into the real-time world of degradation kinetics in the webinar: Degradation in Motion: How Live-Cell Kinetics Drive Degrader Optimization, sharing how dynamic data provides a clearer view of degrader performance than traditional endpoint assays.

Whether you’re exploring your first PROTAC or optimizing a molecular glue series, the expertise offered in Dr. Riching’s presentation gives you actionable insights that will help you connect kinetic data to better therapeutic design.

3D visualization of a protein structure within a live-cell environment, highlighting the interaction site relevant to targeted protein degradation, set against a dark cellular background to emphasize kinetic dynamics.
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How The OceanOmics Centre is Using the Maxwell RSC to Scale eDNA Biodiversity Monitoring

Posted on by Promega

This blog is written by guest blogger Ben Rushton, Application Specialist/Territory Manager at Promega Australia.

When you’re monitoring marine biodiversity at scale, every drop of seawater tells a story. At Minderoo OceanOmics Centre at the University of Western Australia, scientists are uncovering that story through environmental DNA (eDNA)—and automation is helping them listen more clearly.

Laura Missen, a Scientific Officer at OceanOmics Centre, shares how automating their DNA extraction workflow with the Maxwell® RSC 48 system has transformed how they gather and interpret data from marine ecosystems.

(Image credit: Giacomo d’Orlando / Ronin_Lab)
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How Thalidomide and Molecular Glues Are Redefining Drug Discovery

Posted on by Kari Kenefick

Targeted protein degradation (TPD) is a strategy used to selectively remove proteins from cells, rather than simply blocking their activity. Traditional small-molecule drugs work by binding to a protein and inhibiting its function, leaving the protein intact. In contrast, TPD harnesses the cell waste-disposal system—in particular, the ubiquitin-proteasome pathway—to tag the target protein for destruction. Once tagged, the protein is chopped up and recycled by the proteasome, eliminating it from the cell.

Perhaps the best known TPD approach uses PROTACs (proteolysis-targeting chimeras), which are bifunctional molecules: one end binds the protein of interest, and the other recruits an E3 ubiquitin ligase. By bringing the protein and ligase together, the PROTAC triggers ubiquitin tagging and subsequent degradation.

How NanoBRET works image.

Molecular glues achieve the same end result—selective protein destruction—in a different way. Instead of acting as a physical bridge between the protein and the E3 ligase, molecular glues bind to one protein (often the ligase) and subtly change its shape or surface properties, improving interaction with the target protein. This induced fit causes the target protein to be ubiquitinated without a large, two-part molecule like a PROTAC.

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Exploring the Relationship Between IC50 and Kd in Pharmacology

Posted on by Promega

This guest blog post is written by Tian Yang, Associate Product Manager at Promega.

In the realm of chemical probe development and drug discovery, understanding the interactions between drugs/compounds and their targets is crucial. Two frequently used metrics to characterize these interactions are IC50 and Kd, which guide researchers in evaluating the potential of compounds in effecting changes in target function. IC50 offers insights into a compound’s potency by quantifying its ability to inhibit a specific biological activity. Kd provides a measure of the affinity between a ligand and its receptor, reflecting how tightly a compound binds to its target (1). Together, these parameters are instrumental in the early stages of drug development, helping to identify promising candidates by assessing a compounds’s binding characteristics and its observed efficacy.

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Why mRNA Transfection Is Transforming Transient Expression Workflows

Posted on by Shannon Sindermann

Transfection is a core technique in molecular biology used to introduce foreign nucleic acids—such as DNA, RNA, or small RNAs like siRNA, shRNA, and miRNA—into eukaryotic cells. This enables researchers to manipulate gene expression and study cellular processes, disease mechanisms and therapeutic strategies (1).

Advances in transfection technology now support a range of nucleic acid types and cell models. Researchers can pursue transient or stable expression to achieve specific goals: knocking down transcripts, expressing proteins, or probing promoter activity in systems from immortalized lines to stem cells (1).

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An Unexpected Culprit in Heart Disease? Meet Your Gut Microbes 

Posted on by Sara Millevolte

For decades, heart disease–particularly atherosclerosis, a condition characterized by the buildup of plaque in the artery walls–has remained the world’s top health challenge despite major medical advances. Cholesterol and high-fat diets have long shouldered the blame, but new research published in Nature uncovers an unexpected suspect: our gut microbes.  

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ATP-Powered Proteins Beyond Kinases – and Why Helicases Are Stealing the Spotlight

Posted on by Kari Kenefick

This blog was written by guest author Michael Curtin, Senior Product Manager, Small Molecule Drug Discovery.

ATP is the universal energy currency of cells, and thousands of proteins outside the kinase family “spend” it to move cargo, remodel nucleic acids, pump ions, or fold proteins. These ATP-hydrolyzing enzymes—collectively known as ATPases—span functional classes including motor proteins, transporters, chaperones, chromatin remodelers, ligases, and, crucially for genome stability, helicases.

From DNA replication to RNA processing, helicases are essential players. DNA/RNA helicases such as MCM, XPB/XPD, WRN, and members of the DDX family sit alongside AAA+ unfoldases, ABC transporters, and V-ATPases—all drawing on ATP to power their molecular work.

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