Gartel and his colleagues have shown that proteasome inhibitors FOXM1 Transkriptionsaktivit t Expression and suppress in a number of malignant cell lines and may contribute to the anti-cancer effects of proteasome inhibitors. DNA repair, recent research has shown an r For the UPP. In regulating DNA repair by nucleotide excision repair mechanisms such as, repair replication mail and homologous recombination Proteasome inhibitors can these canals le influence by the depletion of the available nuclear ubiquitin, inhibition of proteasome activity to t, which is not a Anh Ufung polyubiquitinated proteins degraded, resulting in DCC-2036 a reduction of the amount released by the ubiquitin cell. This leads to a depletion loss without ubiquitin monoubiquitinated histones in the cell nucleus and thus S changing the DNA-Sch The reaction. Proteasome inhibitors have shown that tumor cells to various anti-tumor therapies, such as radiation inhibitors, and topoisomerase camptothecin, all DNA damage inducing sensitize. Proteasome inhibitors in clinical development bortezomib, an inhibitor of the peptide boronate was to arrive at the first proteasome inhibitor in clinical practice. Increasingly clear from translational research and clinical trials with bortezomib established the proteasome as a novel therapeutic target and legitimate. However, there are restrictions in the use of bortezomib including normal dose-limiting toxicity, t, especially peripheral neuropathy, limited T Activity in solid tumors, resistance and intravenous Sen administration.
This has prompted the development of a new generation of proteasome inhibitors structurally different. In addition to bortezomib, there are currently five proteasome inhibitors in clinical development, three different acids, the structural classes of peptide boronic, Peptide epoxy ketones and lactones. These inhibitors bind either reversibly or irreversibly to the catalytic site in the proteasome. A view of bortezomib with other proteasome inhibitors of the second generation is currently in clinical development is presented below. Bortezomib is a reversible inhibitor bortezomib first affect the activity of t L of the proteasome CT. This compound was Selected from a panel of Boron Acid analogues compared with the National Cancer Institute, the panel 60 cancer cell lines on the basis of his power and cytotoxicity t Searches Hlt. Bortezomib has also been studied in vitro and in vivo in various tumor types, and showed signs of activity t in non-small cell lung cancer, prostate cancer, multiple myeloma and mantle cell and follicular Ren non-Hodgkin’s lymphoma. Bortezomib was particularly active best against multiple myeloma and Phase I to Phase III clinical trials soon CONFIRMS its efficacy in this disease. Bortezomib was approved for third-line treatment of multiple myeloma by the FDA in 2003 and expanded to first-line treatment in 2008, approved for use in mantle cell lymphoma was in 2006. W During bortezomib has significant activity t Monotherapy is their Haupts Chliche use as a means to overcome the resistance and sensitivity to induce a variety of other chemotherapeutic agents. Bortezomib was compared to doxorubicin, thalidomide, melphalan, dexamethasone, a combined