How Thalidomide and Molecular Glues Are Rede๏ฌning Drug Discovery

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 systemโ€”in particular, the ubiquitin-proteasome pathwayโ€”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 resultโ€”selective protein destructionโ€”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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ATP-Powered Proteins Beyond Kinases โ€“ and Why Helicases Are Stealing the Spotlight

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 โ€œspendโ€ it to move cargo, remodel nucleic acids, pump ions, or fold proteins. These ATP-hydrolyzing enzymesโ€”collectively known as ATPasesโ€”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-ATPasesโ€”all drawing on ATP to power their molecular work.

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Matching Luciferase Reporter Assays to Your Experimental Goals

Luciferase reporter assays are highly versatile, but their true power comes when the reporter system youโ€™ve selected is well aligned with your experimental objectives. Whether you’re tracking transcriptional changes or pathway activity, assessing miRNA/siRNA regulation, or using as a readout in CRISPR-based screens, choosing a reporter and detection assay format that fit your specific research goal is critical for meaningful, reproducible results.

You may have already read about how to choose a luciferase reporter assay, but now, we will walk through how to match luciferase reporter systemsโ€”reporter types, detection chemistries, and formatsโ€”to your specific experimental needs. While luciferases like NanoLuc have applications beyond gene expression, this blog focuses on genetic reporter applications and the workflows that support them.

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HiBiT-Based NanoBRETยฎ Assay Sheds Light on GPCRโ€“Ligand Binding in Live Cells

G-protein-coupled receptors (GPCRs) are among the most important drug targets in human biology, mediating signals across nearly every physiological system. But not all GPCRs are equally easy to studyโ€”especially those that interact with peptide ligands. These ligands tend to be flexible, fast-moving, and hard to trace in live cells by standard methods. Historically, radioligand binding assays have filled this gap, offering a way to measure peptideโ€“receptor interactions with high sensitivity. However, these assays are typically performed using isolated membrane preparations or cells under non-physiological conditions, and they donโ€™t allow for real-time or kinetic measurements.

Artistic Image of Hibit Tag

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20 Years of Organ Transplant Testing with Maxwellยฎ Instrumentation

MacKenzie Gartner, Lead Technologist at DCi, operates a Maxwellยฎ instrument.
MacKenzie Gartner, Lead Technologist at DCi, operates a Maxwellยฎ instrument.

For twenty years, the transplant lab at Dialysis Clinic, Inc. (DCi) in Nashville, TN has depended on Maxwell instruments for their automated nucleic acid purification. In fact, the lab was the first to purchase the instrument when it debuted in 2005. Today, theyโ€™ve scaled up to three of the latest Maxwellยฎ Instruments.

โ€œTheyโ€™re great little instruments,โ€ says Christina Sholar, Clinical Supervisor at DCi. โ€œI think this is our third generation, and we still have the original in the basement. We love them.โ€

Christinaโ€™s lab runs critical tests to ensure compatibility between donors and recipients for solid organ and stem cell transplants. With precious samples and urgent demands, they need tools they can depend on for high-quality results. Their Maxwellยฎ instruments help them ensure successful downstream analysis to support important clinical decisions.

Precious Samples, Urgent Timelines

A DCi lab technician adds a sample to a cartridge before loading the Maxwellยฎ instrument.
Hailey, a technician at DCi, loads a Maxwellยฎ cartridge.

Founded in 1971 as a non-profit dialysis clinic, DCi now supports a broad spectrum of kidney health issues, including transplants. The company has also expanded its operations to support organ transplants through federally designated organ procurement organizations. Christinaโ€™s lab runs the tests to ensure compatibility between donors and recipients.   

โ€œWe cover the state of Tennessee,โ€ Christina says. โ€œWe do the typing and antibody analysis for solid organ transplants, and then we follow them post-transplant to see if theyโ€™ve developed antibodies to the donor. We also do stem cell workups and follow-ups.โ€

The lab processes 150-200 samples per week. In addition to managing the high sample throughput, the team also must be available 24/7 for urgent calls when an organ donor passes away.

โ€œWe used to average about 50 donors a month, but thatโ€™s creeping up,โ€ Christina says.

Christina says her team needs a workflow built for speed and minimal hands-on processing. With downstream assays including NGS and qPCR, they also need to trust theyโ€™ll have a high-quality DNA sample to work with. Thatโ€™s what led them to the Maxwell platform in 2005.

Instrumentation for Easy, Reliable Results  

โ€œMaxwell purifications are an easy thing to start new employees with, because they can get quality DNA very easily,โ€ says MacKenzie Gartner, Lead Technologist in Christinaโ€™s lab at DCi. โ€œTechs pick up on it very quickly, and itโ€™s something they can feel confident in doing by themselves.โ€

Twenty years ago, the lab was using manual methods to purify all their nucleic acids. Unlike MacKenzie, Christina remembers those days and admits they werenโ€™t fun. The protocols were labor-intensive, and much more prone to human error. Now, they donโ€™t even teach manual methods anymore.

The DCi lab currently operates three Maxwellยฎ instruments.
The DCi lab currently operates three Maxwellยฎ instruments.

โ€œWhen I came on nine years ago, they were teaching a manual method as backup for the Maxwell instruments, but they never got around teaching it to me because it was needed so rarely,โ€ MacKenzie says. โ€œNow itโ€™s not even in the training materials.โ€

MacKenzie works hands-on with the Maxwell instruments almost every day. The lab mainly uses the Maxwellยฎ Buffy Coat DNA Kit and Maxwellยฎ Buccal Swab DNA Kit. Buccal swabs require 20 minutes of passive pre-processing, but buffy coats can be added directly to the Maxwell cartridges. From there, the automated protocol is only 45 minutes.

โ€œItโ€™s nice that both of them can be run on the same instrument, which gives us flexibility knowing that all three instruments can be available no matter what weโ€™re doing,โ€ MacKenzie adds.

One of the lab's original Maxwellยฎ instruments, still in storage in the basement.
One of the lab’s original Maxwellยฎ instruments, still in storage in the basement.

Christina says the Maxwell instruments provide much cleaner DNA eluates than their past manual methods. This is invaluable for lab efficiency, but itโ€™s even more important with stem cell testing.

โ€œWith stem cells, they may only send one tube but want three or four different tests,โ€ she explains. โ€œWe donโ€™t have room for error โ€“ those samples are precious.โ€

โ€œWe keep the instruments pretty active,โ€ MacKenzie adds. โ€œThat room constantly has their little noises going. But theyโ€™re so dependable โ€“ they donโ€™t take much maintenance, and we can count on having one available even when we get some urgent samples from a donor.โ€

Long-Term Partnership for Success

โ€œPromega is probably our favorite company to work with, as far as support goes,โ€ Christina says. โ€œWe rarely have issues, but when we do, we get great responses very quickly.โ€

As a leader, Christina values strong relationships with her suppliers. Though the labโ€™s sales representative has changed a few times over the past two decades, she says each one has been reliable and helpful in keeping the lab operations running smoothly. The lab has also benefited from regularly scheduled preventive maintenance visits from Promega service engineers.

โ€œOverall, I just love how dependable the instruments are,โ€ Christina says. โ€œWeโ€™re using them all the time. Theyโ€™re truly our workhorses.โ€

All photos credit: DCi


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 offโ€”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 inhibitorsโ€”single molecules that can simultaneously block BET and HDAC activity.

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Avoid the Summertime Blue-Greensโ€” Know about Cyanobacteria Before You Hit the Water

Warning sign reading "ALGAE BLOOM โ€“ NO SWIMMING" posted in a lake with visible green algae floating on the water's surface, surrounded by lily pads and aquatic plants under a clear blue sky.

The weather is warming up (at least in the Northern Hemisphere). There is nothing more refreshing on a hot summer day than a dip in cool lake waters, so people everywhere are digging out their swimsuits and hitting the beach. Unfortunately, the same warm temperatures that drive us to the beach can also cause a potentially deadly overgrowth of blue-green algae โ€”also called harmful algal blooms (HABs)โ€”in the water of our favorite pond or lake.

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Accurate and On-Time: A Look Inside Promega Logistics

Packages move through Kepler Center
Each week, thousands of parcels are shipped to customers from Kepler Center in Madison, WI.

Weโ€™re all used to the convenience of online ordering, whether itโ€™s a last-minute birthday gift or a phone charger delivered overnight. That same ease and speed is what scientists expect when ordering critical reagents for their work. At Promega, we get that. Thatโ€™s why we pledge: Youโ€™ll get what you need, when you need it.

For customers in the United States, any order received by 4:00 pm will be delivered the next day. We measure our success in honoring this pledge using a metric called โ€œorder fill rate.โ€ Our global order fill rate is consistently above our benchmark of 94.5%, sometimes passing 98%.

But how does that actually happen? With thousands of orders leaving our warehouse every week, it takes more than just good intentions. Here’s a look behind the scenes at how our teams deliver on that promise.

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Augmenting Human Capabilities with AI Tools

We hear a lot of stories about AI tools helping people complete tasks more quickly, or automating menial or redundant tasks. However, Promega isnโ€™t just interested in speeding things up. Weโ€™re focused on leveraging AI tools to help us do things better. All over the organization, employees are leveraging large language models (LLMs) and machine learning systems to accomplish things that werenโ€™t possible before, or to make their work more effective against their goals.

Three employees shared their recent successes, including strengthening supervisory skills, scaling up production processes and training new team members. Each of these examples uses AI in a unique way, while still elevating human expertise, creativity and decision-making.

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Lead with Empathy: Supporting Caregivers in the Workplace

This post is guest-written by Diana Clark, Sr Benefits Manager, Promega


Promega Benefits Manager Diana Clark advocates for policies that support the specific needs of caregivers.

My personal caregiving journey began in my late-30s while raising young children and caring for a terminally ill parent. This period gave me firsthand experience into how difficult it can be to balance all of those responsibilities. I learned about the impossible choices caregivers face, and the toll it can take on a personโ€™s physical, emotional and professional wellbeing.

That personal experience has become a cornerstone of my work as a benefits manager advocating for meaningful, compassionate policies that truly support our employees.

At Promega, we believe people bring their whole selves to work. Supporting caregivers isnโ€™t just an act of kindness โ€“ itโ€™s an investment in our people and culture.

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