Miniaturization of Cytochrome P450 Time-dependent Inhibition Screening Using the Echo® Liquid Handler

1 May 2013

As a large number of compounds are screened for ADMET properties against various cytochrome P450 (CYP) enzymes on a regular basis, miniaturization and automation of ADMET assays have become one of the top priorities to manage the cost and labor. This application note presents results from miniaturized time-dependent inhibition assays. The time-dependent inhibition for two of the most abundant CYP enzymes, CYP3A4 and 1A2, were evaluated. The results from the Echo liquid handler method demonstrate fast, reliable and accurate IC50 values.

Echo® 500 Series Liquid Handlers

The Echo® liquid handler revolutionizes liquid handling with acoustic energy. Sound waves eject precisely sized droplets from a source onto a microplate, slide or other surface suspended above the source. This product does not use tips, pin tools or nozzles—completely eliminating contact between the instrument and the liquid. The Echo liquid handler provides powerful benefits: Tipless transfer, resulting in dramatic cost savings Improved information about sample integrity and improved transfer quality through measurement of DMSO hydration level Elimination of the need for calibration through Dynamic Fluid Analysis™ technology, a patented Labcyte process Elimination of cross-contamination, carryover or leachates through non-contact transfer Accurate, precise movement of nanoliter-scale quantities, enabling assay miniaturization and further reducing costs Better results through direct dilution of compounds, an improvement over serial dilution methods Greatly simplified assay development and dilution processes through the flexibility to transfer any volume of liquid from any well to any other well

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ADME-ToxicologyADME-toxicology (ADME-Tox) studies are used in pharmacology and pharmacokinetics to assess the activity/toxicity of drugs <i>in vivo</i> or <i>in vitro</i>. Find bioassays for absorption, distribution, metabolism, and excretion of drug molecules including cytotoxicity, transporter/permeability, metabolism and activity assays as well as hepatocytes and cell lines for ADME. Find the best ADME-toxicology products in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Assay AssemblyAssay Assembly is technique used in drug discovery to develop assays to test the cytotoxicity, genotoxicity, or other activities of a compound on a cell. Assay assembly requires chip assembly, a delivery system and a detection and analysis method. Beneficial features of assay kits or automated systems include high-throughput, high speed and sensitivity and low signal to noise ratio.Cell-Based AssaysCell-based assays are used to monitor the presence, quantity and activities of a desired cellular analyte including drug molecules or biomarkers. This can reveal information on cell health (apoptosis, cytotoxicity, viability and proliferation assays), cell metabolism, cell migration and cell signaling mechanisms. Find the best cell-based assay products, kits and equipment with our peer reviewed product directory: compare products, check customer reviews and receiving pricing direct from manufacturers.Automated Liquid HandlingAutomated liquid handling equipment is used to mix, dilute and dispense allotted volumes of liquid into microplates and other vessels automatically. The robotic, liquid handling arms can dispense from single channel to 3456 multichannel as well as operate nanoliter dispensing, enabling high throughput of samples. Find the best automated liquid handlers in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Liquid Handling WorkstationLiquid handling workstations automate the process of sample preparation, improving accuracy and efficiency. These systems are essential for high-throughput applications in biological, chemical, and pharmaceutical research, reducing human error and increasing reproducibility. Workstations come equipped with robotic arms, pipetting tools, and other accessories to streamline lab workflows. Explore liquid handling workstations in our peer-reviewed product directory; compare products, check reviews, and get pricing directly from manufacturers.CYPCYP3A4Cytochrome P450 AssaysMinimizing Reagent LossInhibitors