be through the respective Tr Regorafenib BAY 73-4506 Compensated ger, and that the two carrier hunter cooperating with each other to prevent ingress of chemotherapeutics to prevent the brain. P gp and BCRP cooperation means that the absence of gp or BCRP or P unrecorded Dinner double a significant increase penetration into the brain of substrates. In BCRP knockout Mice, P gp is alone sufficient to prevent drugs from in the brain. Similarly, k can Into the knockout M Nozzles P gp BCRP alone sufficient to limit the absorption of the drug in the brain. The gr Te improve the brain penetration of two substrates is always seen when both combined P gp and BCRP in knockout mice lacking Pgp, BCRP are.
A look into the mechanism PHA-680632 of cooperation BCRP P gp can, by the relative affinity Th of drug transporters substrate and obtain the rate of expression of the transporter of the BBB. this regard Kamiie et al. LC MS is used to quantify the expression of membrane transporter in the mouse BBB about 5 times h Forth P gp protein levels compared to those of the BCRP. Distinctly Here protein expression at the BBB brand gp P seems the dominant carrier hunter efflux double many substrates Similar affinity Th both P gp and BCRP be. For comparison, due to the lower expression of proteins, BCRP mediated efflux appears to be low, and is shown only in the absence of P or both gp transporter. For example, for a compound with a moderate affinity P t gp are h Here P gp expression levels for a lower affinity t of tears gers which then creates a pronounced Gte effect on the P gp efflux of this compound to compensate BBB.
This is for almost all anti-cancer drugs before, are called with the exception of sorafenib and dantrolene. Both compounds have a much h Here affinity t For BCRP as P gp. Therefore, the dominant carrier BCRP hunter is in the maintenance of these drugs on the brain and the effect of P gp on drug penetration only visible in the BCRP and P gp knockout mouse BCRP. Kodaira et al. P gp BCRP explained explained in more detail Cooperation in determining the net contribution BUREAU each transporter to the total outflow of various drugs on the Pr. The authors have shown that for many substrates double gpmediated P efflux from the brain gr, He served as the BCRP. On the other side was P efflux gpmediated dantrolene 10 lower efflux BCRPmediated dantrolene.
Although these studies were conducted in animal models, it is now clear that BBB Pgp and BCRP expression depends on the species Depends. In this regard, Uchida et al. recently reported that in the human BBB, BCRP protein h Heren P gp protein. LC with MS, the authors determined fmol 8 g of total protein for BCRP to 6 fmol g of total protein for P gp in the human brain capillaries. However, in order to draw a clear conclusion of the absolute values of the transporter proteins On the meaning of each Tr hunter for brain drug delivery is difficult. LC MS Ma exception Total transport