Cell Biology

Residence Time: The Impact of Binding Kinetics on Compound-Target Interactions

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.

During the development of chemical probes or small-molecule drugs, compound affinity (Kd) or potency (IC50) is used to characterize compound-target interactions, to guide structure-activity relationship analysis and lead optimization and to assess compound selectivity.

However, neither parameter provides information on how quickly a compound engages with and dissociates from the target. The dissociation constant Kd reflects the relative concentrations of unbound and bound state of the compound at thermodynamic equilibrium, and while IC50 is an empirical metric that measures the concentration at which a biochemical or cellular process is reduced to half of the maximum value, IC50 values are typically determined when the process is assumed to be at equilibrium or steady-state. For a closed system, like cells in a culture dish, these thermodynamic parameters are quite informative. In an open system like the human body, where compound-target interactions often do not reach equilibrium, the kinetic parameters, in addition to the thermodynamic parameters, are needed to better understand and characterize compound target engagement over time (1,2).

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How Calcium Shapes Cell Communication and Invasion

Posted on by Shannon Sindermann

Platelets are best known for their role in blood clotting, but they also participate in other biological processes that influence how cells communicate and behave. In research models, scientists have observed that tumor cells can interact with platelets in ways that affect how they move and attach to new environments. A recent study by Morris et al., published in Scientific Reports, explored the molecular details behind these platelet–cell interactions and the role of calcium in regulating them.

The Role of Integrins and Calcium

The study focused on integrins, which are surface proteins that help cells anchor to their surroundings and communicate with the extracellular matrix. Two integrins, αIIbβ3 and αvβ3, are particularly important because they mediate platelet–platelet and platelet–cancer cell binding. Their structure and function depend on divalent cations such as calcium, which stabilize receptor conformation and support ligand binding.

When extracellular calcium levels were manipulated, platelet behavior changed in distinct ways.

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Insights from 3D Liver Models: Rethinking Fatty Liver Disease with Hormone Correction

Posted on by Simon Moe

Liver disease is a global health challenge, affecting millions each year. The liver has a remarkable ability to regenerate; however, chronic damage arising from obesity, alcohol, or metabolic dysfunction can lead to irreversible failure. At the University of Edinburgh’s Centre for Regenerative Medicine, Professor David Hay’s lab is developing innovative ways to study liver function and disease using a lab-grown mini-organ. In this blog, we highlight how Dr. Hay’s lab is redefining liver disease research through 3D models that reveal how hormones influence metabolic health.

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What Drives Muscle Fiber Shifts in Obesity and Type ll Diabetes?

Posted on by Kari Kenefick

Skeletal muscle is the body’s main consumer of glucose derived from food.

Muscle Fiber Types
Skeletal muscle is composed of two types of muscle fiber: Type I (slow-twitch) and Type II (fast-twitch).
Type I fibers contract slowly and can maintain contraction over long periods of time. They are rich in mitochondria and myoglobin and are well vascularized. These fibers rely mostly on aerobic metabolism to make the ATP that fuels cells. Type I muscle fibers are fatigue-resistant and efficient—great for supporting posture, distance running, cycling and any activity that needs steady output.

Type II fibers contract quickly, produce more force and power, but also fatigue more quickly. They have fewer mitochondria and less vasculature and rely more on anaerobic pathways like glycolysis (using glucose without oxygen).

Type I muscle fibers are smaller in diameter and generate less peak force but excel at endurance and heat management. Type II fibers are typically larger, produce more force and speed and handle explosive tasks like sprinting, jumping or heavy lifting.

Most muscles are a mix of fiber types, and genetics sets the starting ratio of Type l to Type ll, but fibers are adaptable. With aging and disuse, Type II fibers tend to atrophy more, which is one reason that power declines faster than endurance.

Another distinction important for this story: Type I fibers are more insulin-sensitive than Type II fibers. Additionally, these fiber types differ in different body types.

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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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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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Targeting Epigenetic Regulators in Cancer: The Promise of BET and HDAC Inhibitors

Posted on by Promega

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 off—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 inhibitors—single molecules that can simultaneously block BET and HDAC activity.

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IL-6/STAT3-Regulated Long Non-Coding RNA Is Involved in Colorectal Cancer Progression

Posted on by Michele Arduengo, PhD

Researchers from Wenzhou Medical University in China have identified a mechanism involving long non-coding RNAs (lncRNA) that contributes to colorectal cancer (CRC) progression. CRC is the third most common cancer worldwide and is one of the most lethal cancers across the globe. Understanding the molecular mechanisms that underlie the development and progression of CRC is critical to developing biomarkers to detect it and new therapeutics to treat it. 

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Understanding Wnt Signaling Through β-Catenin Localization in Live Cells

Posted on by Anna Bennett

The Wnt/β-catenin pathway, long studied in the context of developmental biology, has become increasingly recognized for its role in a wide range of human diseases. Its dysregulation has been implicated in cancer, fibrosis, immune modulation, and neurodegenerative conditions—making it a clinically actionable target across diverse therapeutic areas1. In this blog, we cover the fundamentals of Wnt/β-catenin signaling, highlight ongoing research efforts to understand its role in disease, and show how combining live-cell imaging with luminescent assays complements functional studies.

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The Hidden Role of the Immune Microenvironment in ER+ Breast Cancer Resistance

Posted on by Sara Millevolte

Estrogen receptor-positive (ER+) breast cancers are among the most common and treatable forms of the disease. Many patients respond well to a combination of endocrine therapy and CDK4/6 inhibitors—drugs like ribociclib that block the cell cycle and prevent tumor growth. But for up to half of these patients, treatment eventually fails. The tumor adapts and continues to grow, presenting a major barrier to developing more effective, long-term cancer therapies.

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