protein transport functionally active in the luminal membrane of the capillary endothelium of the brain and tears gerproteins which is inactive in the membranes of intracellular Ren vesicles. For example, measuring LC MS both monomer and dimer BCRP only BCRP dimer is the functionally active form. From what we now affects as functionally active protein transport WZ8040 in the luminal membrane of the capillary endothelium of the brain, the administration of drugs through the BBB. Thus, although the total protein expression of BCRP in the human BBB is h Ago as P gp is unm possible to change is said to this point, the most important carrier hunter for drug delivery in the brain of patients.
To make such a statement, we need information about SB-207499 the functional expression of each Tr hunter at the BBB, the local concentration of drugs and drug transport affinity t. P gp BCRP cooperation BBB schl gt Ten. two fundamental reality First, k Can these tears eng significantly adversely Chtigen drug delivery to the brain, which affects its efficiency. Secondly, the combined inhibition of P gp and BCRP is a potentially attractive therapeutic strategy to improve the delivery and thus the efficacy of drugs that are substrates of the central nervous system. Most chemotherapeutic drugs mentioned Hnt clinical failure in the treatment of brain tumors have. Although P gp and BCRP mediated nkt efflux transport cooperation not to anticancer agents Descr, K Nnte the combined inhibition of both Tr hunters have the gr Most influence in the treatment of cancers of the brain, where a slight increase in absorption of brain drug k Nnte significantly improve the anti-cancer efficacy.
In summary, the absence of gp or BCRP P not enough to make the distribution of the brain substrates double KO, but genetic or chemical two tears to improve likes is necessary to significantly increased Hen the absorption of drugs brain P gp BCRP substrate fight against cancer. Thus current research shows that P to cooperate gp and BCRP team instead of BBB and the Pr Prevention of dual substrates to the brain. This has led to a paradigm shift in research transporter Bureau. 4.2 Dual Inhibition of P gp and BCRP at the BBB in collaboration gp and BCRP P of BBB, the development of compounds that are potent inhibitors of both Tr hunters have an advantage.
Elacridar is a dual inhibitor of P gp BCRP has undergone extensive pr Clinical and clinical evaluation. Elacridar has been used in several pr Clinical studies to inhibit P gp and BCRP at the BBB, administered by the distribution of the brain to improve connections simultaneously. These studies have shown that the green Te Erh Increase penetration of the additive into the brain is not limited to P gp knockout animals BCRP, but can also be observed with two inhibitors of P gp BCRP. For example, Chen et al. showed that the brain increased the penetration of dasatinib fa ht spectacular r. on the simultaneous administration of elacridar We have also significantly improved Fem elacridar displayed