Drug transporters are transmembrane proteins that facilitate the transfer of substances in and out of cells and play a substantial role in drug absorption, distribution and elimination. Drug transporters are composed of two major super families: ABC (ATP binding cassette) and SLC (solute carrier) transporters. During the drug discovery and development phases, in vitro assays are important tools to identify substrates and inhibitors of transporters. Understanding the role that drug transporters play in drug disposition can help elucidate emerging associated research areas like transporter biomarkers, assessment and modulation of tissue concentrations, and the effect of diseases on transporter expression and function.
Mediate unidirectional efflux and are primarily active transporters as they directly rely on ATP hydrolysis to pump their substrates across membranes. They play major roles in hepatobiliary and urinary excretion of drugs from the blood to the lumen, intestinal absorption of drugs, and in brain blood barrier penetration of drugs.
Mediate either drug uptake or efflux and can be facilitated transporters or secondary active transporters, which transport drugs using energy produced by the transmembrane movement of other solutes in accordance with their concentration gradient. They play major roles in hepatic and renal uptake, and urinary excretion.
Table 1 Functions of two major transporters superfamilies
Use of optimized and validated in vitro transporter assays during drug discovery and development leads to a greater confidence in their results in determining whether a new compound is a substrate or inhibitor. The concept of transporter method suitability provides a general scheme to improve predictability and reduce variability of the in vitro assays by incorporating assay validation, acceptance criteria, and probe substrates and inhibitors. Such a scheme can potentially improve assay reproducibility and allow in vitro transporter assays to aid in defining a test compound as a substrate or inhibitor of efflux and uptake transporters.
Figure 1 Transporters
CD ComputaBio provides in vitro transporter assays according to your requirements. We have the full range of transporter services to test drug-transporter interactions, transporter-mediated drug-drug interactions, and transporter-mediated toxicity. The most commonly used methods are vesicular transport assays, uptake assays in transfected cell lines, and bidirectional transport assays in polarized cell lines.
Your assay choice depends on the questions you need to address and the physicochemical properties of your compound, with each assay having distinct advantages and disadvantages. CD ComputaBio provides transporters assays for HTS drug screening efforts. Reagents and instrumentation are readily available for your requirements. Please contact us for more service details.
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