Nuclear Receptor Introduction
Nuclear Receptor Profiling & Panels
Nuclear receptors (NRs) act as sensors for various intracellular molecules including hormones and fatty acid metabolites. The effects of these ligands can be understood by the fact that numerous genes involved in the cellular processes, such as general homeostasis, growth, and defense against microbes, are under the control of NRs. By understanding which diseases, pathways and networks each NR participates, it is easier to anticipate the consequences of regulation of unintended targets by a compound of interest. Although the dominant paradigm in drug discovery is to design maximally selective ligands to act on individual NR targets, many effective drugs act via modulation of multiple proteins rather than single targets.
Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This new appreciation of the role of polypharmacology has significant implications for the two major sources of attrition in drug development, efficacy and toxicity. Thus defining the biological niche of each NR as well as understanding overlapping pathways and functions provides valuable context for evaluating a compound’s liabilities and promise.
In order to characterize the selectivity and potential off-target events, INDIGO offers a comprehensive screen of all our cell-based assays to profile your compound(s).
A major focus in the current discovery of drugs targeting nuclear receptors (NRs) is identifying those with the highest selectivity and hence lowest potential for off-target and unwanted effects. Due to regulation of metabolic enzymes by several NRs, there is increasing interest in understanding the potential of drug-drug and drug-nutrient interactions of potential drug leads. INDIGO provides a comprehensive list of optimized, robust and selective whole-cell NR assays, ideally suited for examining selectivity as well as potential drug-drug interactions. By relying on INDIGO’s profiling service and our nuclear receptor experts, you can make those critical decisions on your compounds with the highest degree of confidence.
When you perform NR profiling with INDIGO, we provide you with all the data and analysis you need to make those critical decisions on the fate of your compounds.
- All the raw data for each receptor and mode
- Summary tables and plots of your data for each receptor and mode including non-linear regression analysis, EC50 and peak activity
- Detailed statistical analysis and IBIPlotTM to visualize the chemical-by-chemical profile of activity across all receptors in your study (available upon request)
- All data is secure and confidential
- Ability to study the largest portfolio of optimized, cell-based Nuclear Receptor assays with accuracy, precision and reproducibility
- Unlike biochemical and direct binding interaction systems, INDIGO’s assays can be used to study agonists, antagonists and inverse agonists
- Flexible options with the capability of studying our whole library of assays or choose from predefined panels or create your own
- Rapid turnaround time with a detailed report evaluating your compounds’ efficacy, potency and selectivity
We are the Nuclear Receptor experts and can assist you in in the critical decisions regarding compound liabilities.
Defining the system that each NR participates can be approached in several ways such as sequence similarity, potential disease implication or transcriptional networks. The latter is particularly helpful since it encompasses NRs to which there are no known endogenous ligands (orphan receptors) or have few selective pharmacologic agents to evaluate biological consequences. By choosing a select group of receptors to study (a predesigned panel), it is possible to better understand the biological and toxicologic effects of your compounds. INDIGO has pre-designed several NR panels for you to choose. Of course, you can also design your own panel of receptors (see the Disease State chart) or talk to our experts to assist in developing a plan of study.