challenges of these two tears asked ger for the delivery of chemotherapy in the brain. We check P gp and BCRP. Regarding their r, And the rules of the BBB, and grasp the latest findings on teamwork P gp BCRP in limiting the brain penetration of drugs-cancer 2 P-glycoprotein in brain cancer 2.1 Background 1976 Rudy Juliano and Victor Ling discovered a large Ki16425 Ki-16425 e membrane glycoprotein molecular weight mutant cancer cells apparently Membranpermeabilit Change t ver to chemotherapeutic agents And therefore as P-glycoprotein. Shortly afterwards, it became clear that the P-glycoprotein efflux transporter very m Chtiges ATPdriven active pumps.
Their substrates from cells against a concentration gradient This discovery was revolutionary R because the first explanation: tion for the failure of the treatment provided with resistance to multiple chemotherapeutic agents is Droxinostat a h frequently observed Ph phenomenon in cancer. A few years Sp th, 1989, was recognized P gp expression of proteins in the human BBB and subsequent studies have touched the presence of P gp in the luminal membrane of the BBB dogfish, mouse, rat best CONFIRMS, cat, dog, monkey, pig and cow. Was found beyond P gp in prime Ren brain tumors and is now considered a critical Tr hunters, the opposition expresses many anti-cancer drugs, such as taxanes alkaloids of periwinkle, recognized the etoposide, and the like, anthracyclines, lanafarnib, imatinib , and topotecan. Then P gp was in the middle of the BBB, brain tumor, and drug delivery research for almost two decades. 2.
2 Inhibition of P-glycoprotein in brain tumors A strategy to improve the delivery of brain-cancer drugs directly P gp transport function block at the BBB transporter inhibitors. P was the first inhibitor of gp ZUF Llig 1981 Tsuruo et al, which verapamil, a calcium channel blocker inhibits P gp mediated efflux discovered in resistant tumor cells showed thereby overcoming drug resistance. As a result, over the years, many chemicals on their R Ability to inhibit P gp Selected Hlt was, and developed a number of inhibitors of different t in the potency, selectivity, And side effects. However, only a few compounds were tested for their potential to improve drug delivery to the brain. The first signs that ofprinciple P gp inhibition can be used to treat brain tumors comes from a study in Nacktm Nozzles implanted with intracerebral human glioblastoma U-118 MG.
In this study, Fellner et al. P gp identified as the most important factor in limiting paclitaxel cancer therapeutic cross the BBB and enter the CNS. In accordance therewith, the treatment of M Nozzles with glioblastoma with paclitaxel does not affect the size E of the tumor, but pretreated Mice With the inhibitor of P gp PSC833 erh Hte the brain concentrations of paclitaxel and Tumorgr E reduced by 90. Subsequent studies of the P-gp inhibitors cyclosporin A, elacridar, tariquidar and Co zosuquidar