There is an increasing appreciation of the role that drug active transporters play in the absorption, distribution, and elimination of a wide variety of drugs in clinical use. In this circumstance, Creative Biolabs measures an efflux ratio through monolayer to determine whether a compound undergoes active transport.
Drug transporters play a critical role in drug absorption through active transport. Transporters can be expressed in variety of tissues (like intestine, liver, brain and kidney) and they selectively transport small amount of drugs whose structural are similar to endogenous substances (e.g. ions, vitamins, amino acids). These transporters can be divided into efflux transporters belonging to the ATP-binding cassette (ABC) family and solute carrier (SLC) family that mediate the influx or bidirectional movement across the cell membrane. Creative Biolabs delivers consistent, high-quality in vitro data based on your specific requirements to identify if your compound is the substrate of those transporters.
Figure 1. Schematic model of the major drug transporters in enterocytes of human small intestine. SLC transporters are depicted by open circles and ABC transporters by shaded ovals. Solid arrows indicate the direction of drug transport (Russel 2010).
SLC Drug Transporters
The SLC (solute carrier) family transports a wide range of substrates across cell membrane using diverse energy coupling mechanisms. Many of the SLC family members facilitate the cellular uptake or influx of substrates, either by facilitated diffusion down the electrochemical gradient or by secondary active transport against a diffusion gradient coupled to the symport or antiport of inorganic or small organic ions to provide the driving force.
The main members of the SLC transporters include SLC15 (including PEPT1 & PEPT2), SLC22 (including OATs, OCT and OCTN), and SLCO (OATPs)subfamilies which play a major role in drug uptake into intestine, liver, and kidney and SLC47(MATE) subfamily which mediates drug efflux into bile and urine.
We can provide mammalian HEK293 cells transiently overexpressing a single transporter (PEPT1, PEPT2, OAT1, OAT2, OAT3, OAT4, OCT1, OCT2, OCTN2, OATP1B1, OATP1B3, OATP1A2, OATP2B1, MATE1, MATE2-K, or other transporters). We use scintillation counter (radiolabelled substrates) and LC-MS/MS (non-radiolabelled substrates) for penetration analysis.
ABC Drug Transporters
ABC transporters play an important role in the absorption, distribution, and elimination of drugs.
One of the most important ABC family transporters is P-glycoprotein (P-gp, a well-recognized efflux transporter in many tissues, i.e. brain, kidney and intestine). We use MDR1-MDCK cell or Caco-2 cell to study drug efflux and active transport by P-gp. In addition, we can provide you P-gp inhibition assay to evaluate drug-drug interactions by determinations IC50 and Ki. Our P-gp inhibition assay is full compliance with FDA guidelines
Another ABC member is multidrug resistance (associated) proteins (MRPs) which mediate the transport of organic anionic compounds. MRPs are expressed in intestine, liver, kidney, and other tissues with a barrier function (such as placenta and brain capillaries). We use Sf9 cells to evaluate MRP2 transporter.
We also provide service to evaluate drugs transported by breast cancer resistance protein (BCRP). BCRP was initially discovered in drug-resistant cancer cell lines. It is expressed in the apical membrane of intestine, liver, kidney, placenta, brain capillaries, and stem cell populations. We use Caco-2 cells to investigate bidirectional transport across the cell monolayer. The assay can also investigate the effect of fumitremorgin C on unidirectional transport.
For more detailed information, please feel free to contact us or directly sent us an inquiry.
Reference
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