Receptor Occupancy (RO) Assay

Measuring the receptor occupancy (RO) of a biotherapeutic agent bound to its pharmacological target has become a critical component and an important part of the analysis of drug pharmacokinetics during neuropharmaceutical development. RO analysis helps to determine the minimum biological effect level of biotherapeutics to predict optimal dosage and dosing schedule. RO analysis data also can be used to evaluate drug safety, since the maximum RO over a long period of time has been used as a marker of overdose, leading to serious side effects and toxicity. Creative Biolabs provides reliable and advanced RO Assay services with various novel approaches for our clients all over the world.

Background of RO Model

RO model is an important component of receptor theory in pharmacology. It systematically applies mathematical methods that are often used in enzyme kinetics to the effect of chemical substances on tissues to quantify the activity of drugs on receptors. The relationship between the observable effects and drug concentration is quantified and the drug effect is linked to the proportion of receptors that the drug occupies at equilibrium. The RO model assumes that the magnitude of the drug response is proportional to the amount of drug binding to the receptor, and once all receptors are in equilibrium, the maximal drug response will be triggered.

RO assays can be accomplished simply by measuring the number of cell surface receptors bound to the drug through radiolabeling test compounds or Western Blotting, or by measuring receptor internalization and shedding to obtain more detailed data. The final result is a proportional curve of the unbound or free receptor, total available receptor and/or bound receptor. RO analysis was originally used to evaluate the drug efficacy of targeted tumor cell therapy, and then this method has been widely developed and used for clinical evaluation of drug efficacy and safety. Many studies currently use dopamine D2/3 RO data to support antipsychotic drug development for Alzheimer's disease.

Fig 1. Direct assessment of receptor binding using fluorescently labeled anti-drug antibodies. (Stewart, et al., 2016)

Our Receptor Occupancy Assay Services

Thanks to our professional R&D team, Creative Biolabs can measure the percentage bound to a specific ligand out of the total number of available target receptors, and provide you with reliable, robust, and reproducible RO relationships and duration data to assist you in the prediction and studies of drug pharmacokinetics, pharmacological efficacy, as well as toxicology. Please contact us with our specialist for further information.

Reference

1. Stewart, J.J.; et al. Role of receptor occupancy assays by flow cytometry in drug development. Cytometry Part B Clinical Cytometry the Journal of the International Society for Analytical Cytology, 2016, 90: 110-116.