Drug Repurposing Screens: Redeploying Old Dogs for New Tricks

This blog was written by guest author, Amy Landreman, PhD.

Drug repurposing, identifying new uses for approved or investigational drugs, is an attractive strategy when looking for new disease treatments. Because the compounds have already gone through some level of pre-clinical optimization and safety testing, this approach can reduce risk, reduce cost, and speed up the timeline for further drug development. An additional benefit of this approach is that it can result in new biological insights or a better understanding of disease mechanisms since these compounds usually already have some level of mechanistic characterization. Indeed, there are now a number of compound collections openly available specifically for the purpose of facilitating drug repurposing efforts. For example, the ReFRAME (Repurposing, Focused Rescue, and Accelerated Medchem) library is a collection of 12,000 compounds developed by Scripps Research Center and has been screened to identify novel candidate therapeutics for Cryptosporidium infection (1). The Broad Institute also offers a drug repurposing hub that contains an annotated collection of over 7,000 compounds.

Drug repurposing libraries, although often smaller than novel compound small molecule libraries, are designed for implementation into high-throughput screening workflows in order to efficiently triage compounds for the desired result. Effective compound screens require assays that can be scaled to 384 or 1536-well microplate formats and implemented in batch or continuous processing workflows. The firefly luciferase reaction has been leveraged to create many assays that are well-suited to these types of high-throughput screening approaches. In particular, the generation of “Glow” assays that have stable luminescent signals and homogenous assay design is a good fit. The signal stability allows for multi-plate processing and because the reagent is added directly to cells in culture, pre-processing steps are eliminated allowing for automated workflows. Assay reagents such as the CellTiter-Glo® Cell Viability Assay and the ADP-Glo™ Kinase Assay are commonly used in screening efforts including those done with repurposing libraries.  In addition, there are several firefly luciferase reporter assay reagents such as Steady-Glo® and Bright-Glo™ Luciferase Assays that have been optimized for high-throughput detection of firefly luciferase activity making them well-suited to repurposing screens.

Continue reading “Drug Repurposing Screens: Redeploying Old Dogs for New Tricks”

Tips for Attendees: Making the Most of a Virtual Conference

Today’s blog was written by guest bloggers Tara Luther, Marketing Specialist Genetic Identity, and Allison Suchon, Manager of Tradeshows and Events at Promega.

2020 has been a year of changes for all of us. We’ve learned how to keep in touch while physically distancing. We’ve learned how to work from home with furry coworkers who encourage us to break from the traditional 9–5 routine. We’ve learned how to make changes to our labs to stay safe and productive.

For many of us, this will also be the first time that we attend a virtual conference. While it’s easy to focus on what we’ll be missing by not gathering together, there are advantages to moving to the virtual space. By making the most out of your virtual experience, you’ll be able to walk away with valuable insights, a robust network, and insights that you can use in your own lab.

To help, we’ve put together a list of tips that will help you maximize your experience at any virtual conferences you attend.

Continue reading “Tips for Attendees: Making the Most of a Virtual Conference”

Meeting Customer Needs in Response to Market Dynamics: Responding to the Coronavirus Pandemic

Today’s blog is written by Chuck York, VP of Manufacturing Operations at Promega.

Coronavirus SARS-2-CoV continues to fuel unprecedented demand for COVID-19 related products. Once a term relegated to virology research labs, “coronavirus” is now a household term and a global crisis that has upended lives, disrupted entire economies and shaken our sense of normalcy.

Clinicians, researchers, government officials and the general public are understandably concerned about the availability of reagents for coronavirus testing. At Promega, we are hearing the needs and concerns of our scientific colleagues and partners, and we are doing all that we can to help alleviate them.

At Promega, we are hearing the needs and concerns of our scientific colleagues and partners, and we are doing all that we can to help alleviate them.

As a global company with thousands of products, we have been meeting customer demand in response to market dynamics for decades. Our long-term approach has served customers well. Our efforts to provide support for the COVID-19 response began in early January, with our work with our colleagues and customers in China. We are applying what we’ve learned to propel us forward in the most efficient way now.  

We continue to increase production of all COVID-19 related reagents and instruments due to an unprecedented increase in global demand. Production lines that were running one shift 5 days a week are now operating 3 shifts seven days a week, and we continue to take measures to increase our manufacturing capacity.

Continue reading “Meeting Customer Needs in Response to Market Dynamics: Responding to the Coronavirus Pandemic”

Investigation of Remdesivir as a Possible Treatment for SARS-2-CoV (2019-nCoV)

Remdesivir (RDV or GS-5734) was used in the treatment of the first case of the SARS-CoV-2 (formerly 2019-nCoV ) in the United States (1). RDV is not an approved drug in any country but has been requested by a number of agencies worldwide to help combat the SARS-CoV-2 virus (2). RDV is an adenine nucleotide monophosphate analog demonstrated to inhibit Ebola virus replication (3). RDV is bioactivated to the triphosphate form within cells and acts as an alternative substrate for the replication-necessary RNA dependent RNA polymerase (RdRp). Incorporation of the analog results in early termination of the primer extension product resulting in the inhibition.

 Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. In this view, the protein particles E, S, M, and HE, also located on the outer surface of the particle, have all been labeled as well. A novel coronavirus virus was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019.
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM CDC

Why all the interest in RDV as a treatment for SARS-CoV-2 ? Much of the interest in RDV is due to a series of studies performed by collaborating groups at the University of North Carolina Chapel Hill (Ralph S. Baric’s lab) and Vanderbilit University Medical Center (Mark R. Denison’s lab) in collaboration with Gilead Sciences. 

Continue reading “Investigation of Remdesivir as a Possible Treatment for SARS-2-CoV (2019-nCoV)”