INDIGO Biosciences Blog

Nuclear Receptors in Drug Discovery Research

July 6, 2020

Modern drug discovery involves the identification of screening hits, medicinal chemistry, and optimization of those hits to increase the affinity, selectivity, efficacy/potency, metabolic stability, and bioavailability. This process is time-consuming, costly, and risky. Nuclear receptors are ideal targets for drug discovery. They control a variety of biological and disease processes through the expression of specific genes. Nuclear receptors do this by binding to lipophilic substances known as ligands.

 

Identifying & Evaluating Potential Candidates

Once a disease and target has been selected as an area of research to develop a new novel therapeutic, high-throughput screening is used. High-throughput screening allows a researcher to quickly conduct thousands, sometimes millions, of tests and rapidly identify active compounds, antibodies, or genes that modulate a receptor. Labs often begin this process by utilizing binding assays as they provide a basic yes or no response to understand if a drug candidate may affect the receptor. Many scientists will work with a contract research organization whose lab is already set up to complete high-throughput screening quickly and efficiently.

After narrowing the number of potential drug candidates, compounds need to be further examined to better understand their efficacy and potency in cells. Cell-based reporter assays are designed to quantify nuclear receptor activity and are sensitive to different concentrations of the potential drug, making them ideal for the next phase of discovery research. This step in the drug discovery process allows scientists to learn the EC50/IC50 values of a compound to establish potential recommended dosing levels prior to moving into clinical trials.

 

Detecting Unintended Side Effects

One of the final steps before moving on to ortholog and clinical trials is to test against other nuclear receptors to assess the safety, toxicity, pharmacokinetics, and metabolism of the potential drug.  Nuclear receptors act as a network within the body and a compound which interacts with one nuclear receptor will often affect others. Nuclear receptors are affiliated with multiple different diseases, pathways, and networks, and by testing the compound against a panel of cell-based reporter assays in vitro, scientists can predict and understand potential unintended side effects of a compound.  When researchers believe that there is sufficient information to move forward, animal and human trails can begin.

 

Nuclear Receptor Reporter Cell-Based Assays

INDIGO Biosciences has the largest portfolio of cell-based nuclear receptor assays in the world, helping scientists identify compounds with the highest sensitivity and lowest potential for unwanted effects and off-target responses. The assay utilize firefly luciferase reporter gene technology to provide optimal assay sensitivity and dynamic range when quantifying nuclear receptor activity. INDIGO’s assays provide reproducible data lot to lot about the efficacy, potency, and selectivity of your compounds, with kits delivering results in just 24 hours and team of experts available to perform screening services to help your team move forward with confidence. Learn more about INDIGO’s assay system.

 

Want to Know More?

What to know more about how nuclear receptor can be used as targets for novel therapeutics in drug discovery? Request information from the team at INDIGO Biosciences to learn more about how INDIGO is helping to reduce the time, cost, and risk associated with the drug discovery process.

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