Measure Engagement to Target Proteins within Complexes: Why Context Matters

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.

For target-based drug discovery programs, biochemical assays using purified target proteins are often run for initial hit discovery, as these assays are target-specific, quantitative and amenable for high-throughput screens, allowing for precise characterization of target-compound interactions. However, proteins do not act in isolation inside the cells. Instead, proteins form complexes with other cellular components to drive cellular processes, signaling cascades, and metabolic pathways. Just as the interactions between a target protein and its binding partners can influence the target function, compound engagement with target proteins can vary depending on the protein complex formed.

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What Shelter Dogs Can Tell Us About Emerging Zoonotic Diseases

Posted on by Michele Arduengo, PhD

Why Are Zoonotic Diseases Becoming a Bigger Risk?

As of September 9, 2025, the Worldometer listed the human global population as 8.3 billion people (1). This population growth means that humans will be living and working in previously uninhabited or minimally disturbed environments, increasing interactions between humans, domestic animals, wildlife, and their pathogens. This intensifying human-animal interface heightens the risk of zoonotic disease transmission, where pathogens cross species barriers (from wildlife to domestic livestock or from wildlife to humans), potentially leading to outbreaks and even pandemics.

How Do Urbanization and Climate Change Amplify Zoonotic Threats?

Urbanization, habitat disruption, and climate change further exacerbate these risks by altering ecosystems and facilitating the spread and emergence of vector-borne and zoonotic diseases. Understanding and addressing these threats requires robust surveillance, effective diagnostics, and proactive strategies to prevent and mitigate disease emergence and spread.

In urban areas, public health officials are already using wastewater to monitor known pathogens and identify “hot spots” of activity to predict increases in illness within local populations (2). Animal shelters are another place where there is an opportunity to monitor for emerging infectious diseases that could affect domestic pet animals.

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Polyserine Targeting: A New Strategy Against Neurodegeneration

Posted on by Johanna Lee

Neurodegenerative diseases like Alzheimer’s are marked by the accumulation of misfolded proteins that wreak havoc on neurons. One of the most notorious culprits is tau, a structural protein that, in its diseased form, clumps together into aggregates that spread throughout the brain. These aggregates interfere with normal cellular processes, leading to memory loss, behavioral changes, and other devastating symptoms. Preventing tau aggregation is therefore a key strategy for slowing the progression of these symptoms.

What if we could recruit molecular “helpers” to stop tau from accumulating?

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A New View of Protein Degradation with HiBiT and Live Cell Imaging

Posted on by Anna Bennett

Targeted protein degradation (TPD) is an emerging drug discovery strategy that offers an entirely different approach to tackle disease-relevant proteins, including classic “undruggable” targets. Instead of inhibiting protein function, small molecules like PROTACs and molecular glues co-opt the cell’s own ubiquitin-proteasome system to eliminate specific proteins altogether. But as this targeted approach gains traction, it also challenges existing methods for validating compound activity.  

How do you confirm that degradation is happening in a biologically-relevant system? Can you validate protein degradation in real-time?  

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Exploring How NEAT1 Shapes Granulosa Cell Function

Posted on by Shannon Sindermann
Granulosa Cells

Granulosa cells (GCs), which surround and support developing oocytes, play a critical role in estrogen production, follicle maturation and overall ovarian health (3). Their ability to regulate hormone production and cell survival makes them a central focus in studies of ovarian biology.

A recent study investigated how the long non-coding RNA (lncRNA) NEAT1 regulates GC function and mapped a pathway that links NEAT1 expression to cell proliferation, apoptosis and hormone production (1).

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At the Forefront of Biologics Characterization: Insights from Promega R&D Scientists 

Posted on by Tera Madigan Ogorazalek

As biologics grow more complex, so do the tools required to understand, validate, and ensure their quality. From monoclonal antibody cocktails to antibody-drug conjugates (ADCs) and cell therapies, developers are navigating new frontiers in potency, purity, and functional characterization. 

Promega’s R&D scientists have been actively contributing to this evolving dialogue through respected industry platforms like BioCompare and BEBPA. Through ongoing collaboration with industry experts, Promega scientists are developing innovative assays and strategies that address the complex challenges of biologics development and quality assurance. 

This article highlights key takeaways from five recent publications featuring Promega experts and collaborators, with insights spanning from early research to quality assurance in manufacturing. 

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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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