Classifying Nuclear Receptors
Benefit of Screening Compounds Based on Functional Classification
Although a dominant idea in drug discovery is to design extremely selective compounds to act on individual nuclear receptor targets, many effective drugs act by affecting multiple receptors rather than a single target. Research in systems biology is revealing a network structure that strongly suggests selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This has significant implications for the two major sources of attrition in drug development: efficacy and toxicity.
With nuclear receptors involved in so many cellular functions it is important for drug discovery researchers to understand a compound’s entire nuclear receptor profile. This enables the researcher to understand not only the on-target effects, but also off-target effects including the potential for drug-drug interactions. With information on the full nuclear receptor profile of a compound based on functional classifications, it becomes much easier to make critical decisions on that compound’s fate. While there are seldom clear black-and-white answers on the best candidate to move forward to clinical trials, the information provided in a profiling screen using functional classifications can provide valuable context for evaluating a compound’s promise and liabilities.