Environmental Monitoring for Endocrine Disrupting Chemicals [and the importance of utilizing bioassays]

Endocrine disrupting chemicals (EDCs) are a class of pollutants that has garnered a lot of attention. These are specific chemicals that disrupt or interfere with elements of endocrine signaling, a critical system that controls metabolism, growth, tissue, reproduction, mood, and other factors and functions in the human body. Depending on the type and outcome, EDCs can impact puberty, immune function, stress, weight, bone health, and more. Some common examples of sources of EDCs are:

Endocrine Disrupting Chemicals and Environmental Toxicology

Environmental toxicology is a multidisciplinary field of science concerned with the study of the harmful effects of various chemical, biological, and physical agents on living organisms. Environmental toxicologists study the effects of toxicants at various concentrations in labs and try to understand the potential for the bioaccumulation in food webs, including our own food supply. Harmful effects of chemicals like DDT and pollutants, insecticides, pesticides, and fertilizers have been found to affect organisms and their communities by reducing species diversity and abundance. These changes in population dynamics then affect the ecosystem by reducing its productivity and stability.

Problems within Drug Discovery: Understanding Drug-Nutrient Interactions [What is a DNI and how Nuclear Receptor activation can be responsible]

Many compounds in the drug discovery process will be impacted by drug-nutrient interactions (DNI) and because of this, have the possibility to fail in clinical trials or have subsequent pharmacokinetic consequences. Xenobiotic nuclear receptors are known to play a significant role in DNI’s. Understanding what DNI’s are and knowing if they will modulate a drugs bioavailability can be important to success in clinical trials, as well as preventing potentially fatal drug-food and drug-herb interactions.

Nuclear receptors and the Microbiome: Does the road to happiness go through the gut?

The microbiome or microbiota are the terms used for the microbes that live on and inside the human body. Trillions of microorganisms make up the microbiome including bacteria, fungi, parasites, and viruses. It is estimated that there are more microbial cells than human cells in the body and the majority of these microbes reside in the gut. There is a growing amount of research that has recently changed our understanding of the microbiome from being just a collection of symbiotic organisms to actively participating in a bidirectional communication system called the gut-brain axis.

CB1R & Drug Discovery: More Than a Feeling

The endocannabinoid system (ECS) is a complex cell-signaling system made up of cannabinoid receptors and the endogenous lipids called endocannabinoids that bind to them. This system was identified in the early 1990s with the cloning of the G-protein coupled receptors (GPCR) Cannabinoid Type 1 Receptor (CB1R) and Cannabinoid Type 2 Receptor (CB2R), as well as the identification of endogenous cannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG).

Designing Safer Pharmaceutical Leads Through Discovery Toxicology

Traditional toxicology practices focus on characterizing a single compound in regulatory GLP toxicology studies over a long period of time directly prior to clinical phase 1 trials. By this time, large amounts of time and resources have been invested into finding a single drug candidate. If a liability is found, researchers are left deciding if the benefits outweigh potential liabilities or if they need to start over, having spent time and resources on that single candidate. With late-stage failures due to toxicity continuing to be a primary cause for compound attrition, incorporating predictive in vitro testing into the discovery process is essential for those working in drug discovery.

To Be or Not to Be: How Nuclear Receptor Profiling Can Determine the Fate of Your Compounds

Nuclear receptors act as transcription factors that mediate the effects of hormones, drugs, and other xenobiotics by regulating the expression of specific genes involved in many cellular functions including development, reproduction, and metabolism. The target gene and protein expression patterns of nuclear receptors and their physiological effects create a network that can be monitored by multimodal approaches, such as systems biology. Therefore, defining the biological niche of each nuclear receptor and understanding their overlapping pathways and functions can provide value to discovery researchers when evaluating a potential compound’s promise and liabilities.

Bioluminescence vs. Fluorescence: Which should I choose to assay my compounds?

When looking to perform in vitro cell-based target validation, pathway analysis, and compound screening there are several types of assays to choose from. One question you might ask when evaluating different cell-based reporter assay technologies is, what is better for my research: an assay system that uses fluorescence or an assay system that utilizes bioluminescence? Both technologies can provide researchers with valuable data so let us weigh their advantages and disadvantages.

What is the Nuclear Receptor Superfamily?

The nuclear receptor superfamily is a group of intracellular transcription factors that directly regulate gene expression in response to lipophilic molecules. These receptors are found in metazoan organisms such as nematodes, insects, and vertebrates. Nuclear receptors affect a wide variety of physiologic functions including development, reproduction, and metabolism and are associated with diseases such as Alzheimer’s, cancer, and diabetes.

Common Ortholog Models & Their Use in Drug Development Research

An animal model is a non-human species that has been widely studied and used during research to help understand biological processes in a laboratory setting. The use of animal models as human surrogates has provided a great deal of information about physiology and disease with over 150 Nobel Prizes awarded in physiology or medicine to professionals utilizing animal models for their research.

The primary reason for the use of animal models is the evolutionary principle that all organisms share some degree of relatedness and genetic similarity. Vertebrate models in particular are useful as human surrogates in drug discovery and medical research due to their more common ancestry. Though there are many vertebrates that could be used, a few are more common in research than others.