The presence of the superfamily members of the ATP binding cassette (ABC) transporters is well established as the main cause of multidrug resistance, since they efflux therapeutic compounds from cells and reduce the intracellular drug levels.
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Ready-to-use efflux proteins for BBB assays
This efflux transporter is expressed in tissue barriers (e.g brain, intestine, placenta) and excretory organs (kidney and liver) where it exerts a protective mechanism by pumping out of the cells and into the blood, bile and urine compounds potentially toxic.
In particular, in the brain, MDR1 is expressed in the apical membrane of endothelial cells where it avoids drug accumulation in the brain enhanced by its broad substrate specificity. Blocking of this efflux transporter alters drug pharmacokinetic parameters and tissue distribution of drugs, increasing drug half-lives and toxicity effects. In fact, the most pronounced pharmacological effects of MDR1 inactivation were seen in the brain, which indicates the important role of MDR1 to prevent compound permeability in the CNS.
Like MDR1, the breast cancer resistant protein (BCRP) is an efflux transporter that belongs to the ATP-binding Cassette Family (ABC) family. Despite BCRP is expressed in a wide number of tissues, there is evidence that this transporter is relevant as one of the major drug transporters involved in clinically relevant drug disposition in the CNS.
BCRP which is more prominent express in humans than MDR1 is found to work cooperatively with MDR1 to restrict compound penetration into the BBB. Therefore, it may happen that the inhibition of BCRP does not prevent the permeability through the BBB of those molecules that are co-substrates of both transporters.
ReadyCell Blood Brain Barrier kits
We help you determine the suitability of your compound to cross the BBB
It is recommended to assess the in-development molecule interaction to P-gp and BCRP receptors to understand the pharmacological route and optimize clinical stages.
CacoReady, and PreadyPort MDR1 and PreadyPort BCRP are three assay-based kits that can be used to identify whether new molecular entities are MDR1 or BCRP substrates/inhibitors.
Frequently Asked Questions
How does the permeability of the BBB differ from that of intestinal barrier?
Blood brain barrier is composed by different cell types (endothelial cells, perycytes and astrocytes). Endothelial cells which line up the brain capillary blood vessels are polarized and present efflux transporters and poorly characterized uptake transporters at the apical and basal membrane which aids BBB to maintain brain homeostasis. It has been reported that, unlike intestinal barrier, BBB prevents the diffusion of > 98% of small-molecule drugs and most of the large biologic therapeutics.
Is CacoReady a representative model of the BBB?
CacoReady model is a good alternative to study BBB permeability despite their epithelial origin since Caco-2 cells form a tight barrier with an electrical resistance above 1000 Ω x cm2. In addition, polarized Caco-2 cellsalso express the MDR1 and BCRP efflux transporters that are present in the luminal site of the brain endothelial cells.
Is the quality control data specific for each kit?
Yes, we provide a concrete quality control for each batch so the customer can have a reference for the kit both in pre-shipment and post-shipment.
Does ReadyCell shipping medium affect cell lines?
No, ReadyCell’s Shipping Medium consists of a semi-solid culture system specifically designed to preserve cells at room temperature (15-25ºC). This medium maintains a suitable physicochemical environment, keeping adequate moisture conditions for cellular homeostasis and forming a protective cushion that protects cell integrity and functionality during long-distance shipments and up to seven days.
What do the current regulations establish on the basis of BCRP and MDR1 transporter tests?
According to regulatory agencies, the identification of P-gp and BCRP substrates and inhibitors during CNS drug development is a regulatory requirement to circumvent potential clinical drug-drug interactions and nonlinear pharmacokinetics.