Cytochrome P450 Inhibition: Old Drug, New Tricks

multiwell screening plate and various pills on a table

Cytochrome P450 (CYP) inhibitors are often used as boosting agents in combination with other drugs. This drug development strategy is front and center for Paxlovid, the new anti-SARS-CoV-2 treatment from Pfizer. Paxlovid is a combination therapy, comprised of two protease inhibitors, nirmatrelvir and ritonavir. It significantly reduces the risk of COVID-19 hospitalization in high-risk adults and is ingested orally rather than injected, which is an advantage over other SARS-CoV-2 treatments, such as Remdesivir.

Nirmatrelvir was originally developed by Pfizer almost 20 years ago to treat HIV and works by blocking enzymes that help viruses replicate. Pfizer created another version of this drug to combat SARS in 2003, but, once that outbreak ended, further development was put on pause until the advent of the COVID-19 pandemic. After developing an intravenous form of nirmatrelvir early in the pandemic, Pfizer created another version that can be taken orally and combined it with ritonavir.

When ritonavir was originally developed, it wasn’t considered particularly useful because it metabolized so quickly in the body. Now it is recognized as a pharmacokinetic enhancer in combination with other drugs. Ritonivir inhibits CYP3A4, an enzyme which plays a key role in the metabolism of drugs and xenobiotics. By inhibiting CYP3A4, ritonivir slows the metabolism of other drugs. In the case of Paxlovid, this allows nirmatrelvir to stay in the body longer at a high enough concentration to be effective against the virus. This ultimately means that patients can be given lower doses of the drug with reducing efficacy.

Diagram of Nirmaltrelvir mechanism of action.
Nirmatrelvir inhibits the viral 3CL protease, so that functional, smaller viral proteins cannot be produced.
Continue reading “Cytochrome P450 Inhibition: Old Drug, New Tricks”

Volunteering. A Celebration of Service, Community and Connection

Promega Madison employees volunteering to gather trash from roadside ditches.
Promega Madison employees gather trash from roadside ditches.

Volunteering is willingly giving your time and effort without expecting something in return. The month of April is volunteer month, and April 20 is national volunteer recognition day, so we are taking this chance to celebrate volunteers and the work they do that benefits us all. Fundamentally, volunteering is about service to others, but that service can take on many different forms. Promega recognizes the benefits that volunteering brings to our employees as well as our local and global communities. Our Promega in Action program offers Madison-based employees the chance to volunteer their time and talents; applicants get up to 40 hours of extra paid time off to work with the charity or organization of their choice.

Continue reading “Volunteering. A Celebration of Service, Community and Connection”

Studying the Genetic Basis of Type 2 Diabetes with An Automated Maxwell® Workflow

Blood collection tubes in a rack. Researchers are learning more about  Type 2 diabetes

Over the past few decades, the prevalence of diabetes has been on the rise. According to the WHO, 422 million people worldwide have diabetes, causing an estimated 1.5 million deaths every year. Among those with diabetes, 95% have type 2 diabetes—which is caused by the body’s resistance to insulin. It is known that risk factors for type 2 diabetes include older age, excess weight, poor diet and family history. However, the precise genetic basis of type 2 diabetes is still largely a mystery.

Dr. Mark McCarthy’s lab at the Oxford Center for Diabetes, Endocrinology and Metabolism (OCDEM) focuses on understanding the genetic causes of type 2 diabetes. Identifying which genes contribute to type 2 diabetes could provide opportunities for developing new therapeutics. Chris Grove, former lab manager in Dr. McCarthy’s lab, explained how they have approached this challenge.

Continue reading “Studying the Genetic Basis of Type 2 Diabetes with An Automated Maxwell® Workflow”

Small Wins, Personal Commitment and Concrete Solutions Add Up to Big Victories in Sustainability

Sustainability. Maybe it is your way of life, or you feel like it is a buzzword used and abused. Perhaps you are tired of hearing about it or convinced that society doesn’t do enough. Well, welcome to Switzerland, the country of Heidi, of mountains and chocolate, and where many are passionate about their environment and fight to preserve it. The team of Promega Switzerland is no exception. Take the General Manager, Mauro Ciglic, for example. He is someone who cares about people, nature, and the environment in the broadest sense. For him, sustainability is an attitude. It’s about questioning one’s lifestyle, behaviors, and habits, reflecting on what one can do personally, and continuously challenging oneself to be and do better for others and the environment. Mauro is aware that economic, social, and environmental aspects are intertwined and that changes in the environment, good or bad, directly impact people, thus society at large. As the person responsible for the Swiss Branch of Promega, Mauro can bring positive change using the company’s financial strength and workforce. He focuses on the opportunities and not the challenges and, with the team, works hard to bring concrete solutions.

“One of the hardest things for people to wrap their heads around tends to be the idea that small wins add up to big victories. However, if we want to make a big difference for the future of our planet and its people, we have to overcome our indifference towards so many small things in life.”

– Mauro Ciglic, General Manager, Promega Switzerland
Continue reading “Small Wins, Personal Commitment and Concrete Solutions Add Up to Big Victories in Sustainability”

Take a Break, Take A Walk!

Elderly father adult son and grandson out for a walk in the park.

For many of us, we’re used to getting our steps in when walking from one meeting room to the next. However, since the beginning of the COVID-19 pandemic, we shifted to new communication modes. Meetings transitioned to simply clicking from one zoom to the other, increasing the amount of time we stay sedentary. For those who are still working remotely, this is a reminder to make time for movement! Contrary to how long periods of sitting have negative effects on the body, walking has a long list of benefits. In the spirit of National Walking Day, here are some reasons why you should take a break and take a walk.

Continue reading “Take a Break, Take A Walk!”

GloMax® Instrument and NanoBiT® Technology Pave the Way for New Research Lab

Dr. Alsulami and the GloMax® Navigator  in his new research lab.

When setting up a new research lab, many researchers opt to outfit their new space with the technology and materials that got them through their academic studies. After graduating with his PhD from the University of Wisconsin-Madison, Dr. Tawfiq Alsulami will be traveling with a GloMax® Navigator Microplate Luminometer across the globe to continue his work as Assistant Professor in the Department of Food Science and Nutrition at King Saud University. Dr. Alsulami and his new lab at KSU will be using the NanoBiT® system to develop novel assays for the future of food testing.

Dr. Tawfiq Alsulami answered a few of our questions regarding his upcoming research at KSU and offered a few pieces of advice to new labs. Read the Q&A below:

Continue reading “GloMax® Instrument and NanoBiT® Technology Pave the Way for New Research Lab”

iGEM Team Explores Regenerative Spinal Cord Treatment with Promega Support

Today’s blog is written by KCL iGEM Team Leaders Alya Masoud Abdelhafid and Luke Bateman. Both in their third and final year at King’s College London, Alya is completing a BSc in Nutrition and Luke a BSc in Biochemistry.  

Every year, the International Genetically Engineered Machine competition (iGEM) offers high-school, undergraduate and post-graduate students the opportunity to conduct independent research using synthetic biology and genetic engineering to develop solutions to local and global problems.

More than 350 teams from around the world participate in iGEM, which culminates in a presentation at the global iGEM Giant Jamboree, attended by more than 6000 people every year. Here, novel research is presented amongst pioneers in synthetic biology, and outstanding projects are awarded prizes for their contribution to the greater scientific community. iGEM teams consistently produce ground-breaking solutions to modern challenges, many of which facilitate the development of multimillion-dollar companies and start-ups.

We are the King’s College London (KCL) iGEM team and are honored to be involved in the innovative and prestigious iGEM community.

Continue reading “iGEM Team Explores Regenerative Spinal Cord Treatment with Promega Support”

Avian Influenza H5N1: From Poultry to Cattle, How Livestock is at Risk with Current US Outbreak

Updated June 24, 2024

In January 2022, the state of South Carolina reported a case of highly pathogenic avian influenza in a wild bird—the first detected case of this virus subtype in the United States since 2016, likely introduced from Canada late in 2021. Since then, the virus has spread across the U.S., affecting both coasts with multiple separate introductions. As of 2024, this outbreak continues to cause significant issues, and has even reached dairy cows in Texas, Kansas, Michigan, New Mexico, South Dakota, Idaho, North Carolina, and Ohio.

Continue reading “Avian Influenza H5N1: From Poultry to Cattle, How Livestock is at Risk with Current US Outbreak”

Using Tumor-Produced Neoantigens to Treat Lynch Syndrome

Lynch syndrome, named for American physician Dr. Henry T. Lynch, is a hereditary condition that causes a predisposition to several types of cancer, most commonly colorectal but to other types as well, including ovarian, endometrial and stomach cancer. The root of this disorder lies in a genetic defect known as DNA mismatch repair deficiency (or dMMR), which affects the process by which mistakes are repaired when our DNA is copied during cell division. People with Lynch syndrome can have up to an 80% increased lifetime risk of developing colorectal cancer, and are more susceptible to developing colorectal and other types of cancers at an earlier age. Accounting for 3-5% of all colon cancers, Lynch syndrome is an excellent target for preventative treatment, like a vaccine. Research exploring a Lynch syndrome vaccine seeks to harness the body’s innate immune response to target tumor cells and has yielded promising results.

Person receiving a vaccine. Lynch syndrome, a hereditary condition that causes a predisposition to several types of cancer is an excellent target for preventative treatment. Read more about how researchers have recently explored vaccines for Lynch syndrome
Continue reading “Using Tumor-Produced Neoantigens to Treat Lynch Syndrome”

Cultured Meat Viability Increases in Biotech

Cultured meat grows in a plastic dish in laboratory conditions.

The biotechnology industry has been powering through barriers standing between the lab and the dinner plate as cultured meat advances toward the market. Challenges like scaling up the technology and getting products to the market are significant, but future food demands are an even bigger obstacle. Earth’s population is projected to reach 10 billion people by 2050. Our current agricultural practices will not be able to meet the food demands. Therefore, we need to find alternative ways to produce food–like “growing” it in the lab.

Continue reading “Cultured Meat Viability Increases in Biotech”