gp inhibition increased brain levels of paclitaxel Ht. It has been shown that elacridar tariquidar and not specific inhibitors of P gp, but also for h BCRP.A inhibit Heren concentrations recent study also showed that oral administration twice a week reduced the new cooperation HM30181A P gp inhibitor with paclitaxel Tumor volume AMG-208 K1735 melanoma brain metastases and glioblastoma U MG 87 in animal models of cancer. Together improved direct P gp inhibition drug delivery brains of some anti-cancer drugs and treatment of brain tumors in animal models. There are currently no reports on the use of inhibitors of tears eng exp Hnt in brain tumors. However tariquidar is currently in a Phase I clinical trial is underway to treat brain tumors in other types of cancer in children.
So it remains to be seen whether the strategy transporter inhibition can be translated as an animal model for the patient. Therefore, the search for the m Most powerful, efficient and selective inhibitors of Pgp. 2.3 Target Rolipram P gp Rules In this article we will be well on the pathways P gp and BCRP affect the blood-brain barrier and tumor blood into brain tumors and cancer stem cells in the brain comment which are used for the delivery of chemotherapeutic agents . improve In this context, the purpose of the targeted regulation Tr hunter downregulate expression or transporter activity is t And functionable Hig that the outflow men Reduced from drugs and overcome drug resistance. The field of regulation of BBB transporter is relatively new and only a few studies have been conducted.
The first study shows the down-regulation of P gp BBB in 2004, ver Ffentlicht. This study of AND 1 signaling by the ETB receptor, NOS, and PKC, the rapid decline in P gp activity t In isolated rat brain capillaries focused. Another report showed that BBB P Gp by inflammatory mediators LPS, TNF and AND 1, TLR4 activated TNFR1, the ETB receptor, NOS, and PKC, leading to a reduction in the activity of P gp t regulated. In a follow-up study, Rigor et al. identifies that PKC beta isoform of PKC down-regulation of P-gp activity t in this direction. More importantly, this study provides proof of principle that targeting PKC increased beta Ht absorption of verapamil brain Pgp substrate. In another study, Hawkins et al. one similar observation using the Vaskul Ren endothelial growth factor.
It was shown that VEGF activity P gp t in the rat brain capillaries reduced the activation of Src 1 and flk, probably by Src phosphorylation of caveolin mediated first This finding means that P gp activity t Serious k Nnte in pathological states Ends with increased Htem brain expression of VEGF and VEGF-Src signaling BBB associated reduced to k Nnten targeted to P gp activity Reduce t . Together, the two signal paths are identified, which are used to regulate the activity of T Downward P gp transport at the BBB, a inflammat for signaling