Puracyp services
Induction of Transporters Services
The new FDA draft guidance suggests that inducers of transporters be identified during drug development. The guidance states “activation of nuclear receptor assays may be used as an initial evaluation of the induction potential of an investigational drug on transporters”. To that end, Puracyp has developed nuclear receptor activation technology for monitoring P-glycoprotein induction. Assays available include CAR and/or PXR activation to identify compounds that induce P-glycoprotein.
Multiplex Analyses Services
Puracyp’s cell lines can be used in a multiplex fashion that includes nuclear receptor activation data, cellular toxicity of test compounds, and to determine P450 metabolism of a luminescent substrate, such as P450 Glo™. Assessing P450 activity in Puracyp’s cell lines provides information to identify compounds that are both inducers and inhibitors. All of this information can be obtained in a single well.
Nuclear Receptor Screens Services
Puracyp offers single assays or panel screens at a discounted price. Our panels are designed to address the FDA’s recent guidance that CYP2B6, CYP1A2 and CYP3A4 induction by NCEs be evaluated. Puracyp’s cells contain the promoter/enhancer of these three P450 enzymes in addition to either CAR, AhR, or PXR. Panel screens are also useful for examining species differences in P450 induction and for toxicology studies using orthologs of human nuclear receptors. An example of results obtained in human cell lines utilizing our panel screen for PXR, AhR and CAR are shown below.
Basic Study Design Services
Our basic study design includes 6 concentrations in duplicate that can be used to calculate EC50 values (see figure below). Also included in the study results are positive and negative (solvent) controls and cell viability (reports toxicity of the test compound). A sample screening report is shown here. Once you receive your data, here is an explanation for interpreting the results.
Custom Designed Panel Assays Services
Mix and match any receptor or species ortholog to develop your own nuclear receptor activation panel. An example of the available assays to use in your study design are shown below.