Pharmacological and pharmaceutical properties
of PD compared to 184,352 confinement, Lich more power for the inhibition of MEK and h Here bioavailability and increased AC480 BMS-599626 FITTINGS metabolic stability t. PD 0325901 has a Ki value of 1 nM to MEK1 and MEK2 in vitro kinase assays. PD 0325901 inhibits the growth of cell lines that increased in response to signaling pathways Ht proliferate Raf MEK ERK. Clinical studies with PD 0325901 documented successes and side effects. Pfizer has suspended evaluation in clinical trials. This may be partially m on the design of clinical trials of MEK inhibitors May not contain suitable for treating all types of cancer. MEK inhibitors may be appropriate to only those types of cancer, the treat proliferate in response to activation of the ERK pathway Raf MEK.
Moreover, it may also be important to include a chemotherapeutic agent or radiation, cancer, to induce cell death. Raf is a target of therapeutic choice upstream Is rts of MEK. Sun Targeting Chrysin MEK is an approach to target tumors contain genes activated RAF. BRAFV600E mutation is present in about 6 to 8 human cancers. Interestingly, mutations in the BRAF cancer about 5 that are not V600E. The effects of PD 0325901 were examined in tumor models related BRAFV600E where genetically modified nozzles M exprimieren Normal B Raf before. Cre-mediated recombination, according to which they express RafV600E B in physiological concentrations If B RafV600E was induced developed Mice lung tumors k Nnte be inhibited by PD 0,325,901th In contrast, M Usen with vehicle alone developed adenomas treated.
This model shows that in some cases F, MEK inhibitors, in order to give good results, the therapy is a cytotoxic drug such as MEK inhibitors are cytostatic and often comprise once the MEK inhibitors are removed, so that the tumor can in resurface. There are no current therapies for HCC. And targeting signaling pathways in HCC was considered as an approach to target HCC. CHC people have a gr Ere expression and increased Hte activity T MEK1 and ERK1 Close 2 2 relative to non-neoplastic liver S. entered via expression of activated MEK1 in HCC HepG2 cells Born improves tumor growth in vivo. On the other hand, have pr Clinical studies, the potential of MEK inhibition of cell proliferation and Tumorigenit Demonstrates t suppress of hepatoma. Huynh et al.
recently reported that blocked the treatment with human xenograft HCC Selumetinib ERK1 activation 2 reduces tumor growth in vivo, and induced apoptosis. Moreover, targeting MEK with PD 0325901 has in vivo chemopr Preventive effect on HCC development in animal models. Using transgenic Mice in which TGF liver cancer induced by diethylnitrosamine treatment Therefore, the MEK is a potential therapeutic target for HCC. RDEA119 described an inhibitor of MEK, recently developed by Ardea Biosciences. It is a highly selective inhibitor of MEK, a selectivity t Of 100 times in the inhibition of the kinase in a panel 205 kinases shows. In contrast, in the analysis of specificity T Meanwhile, other recently developed kinase MEK inhibitors also inhibit Src kinases and RON. There are at least two molecules of ERK cascade regulates Raf MEK ERK