In general, all drugs with 5 co CYP3A4 inducers such as anticonvulsants and corticosteroids Should be used with caution and appropriate alternatives Amonafide AS1413 will be replaced if possible m. Imatinib is a weak inhibitor of CYP2D6 and CYP2C9. Therefore medicines metabolized by these enzymes are used with caution. Imatinib has also been shown to inhibit in vitro glucuronidation O, m May receive by Erh Hen the effect of acetaminophen. Resistance to imatinib resistance patterns Basically there are two types of resistance to imatinib: Prim rwiderstand defi ned as a lack of response to treatment with imatinib anf ngliche. Acquired or secondary resistance re: Losing the benefi t of imatinib after anf nglichem response. In case of insufficient clinical studies imatinib was in h Hematological, cytogenetic, molecular or resistance divided.
The molecular mechanisms of resistance mechanisms to imatinib in CML as a pr Clinical models of imatinib-resistant cell lines and in primary Another patient samples examined. In principle, the absence of embroidered LMC caused by three v Llig different biological mechanisms by treatment with imatinib. Imatinib vers umt, The Kinaseaktivit t Inhibit the Bcr Abl effectively. Growth AEE788 and survival of the malignant clone is independent Ngig of Bcr-Abl kinase activity t. The availability of drugs in the cell is not sufficient to Bcr-Abl kinase activity inhibit t. Target resistance hangs Despite continued treatment with imatinib, the kinase activity remain t and activation of downstream target Bcr Abl high. This can be caused by different mechanisms.
Highest Zun Was reinforcing Stronger cation of bcr abl gene and therefore produce a gr Ere amount of protein in Bcr Abl models of cell lines for resistance to imatinib Selected Observed hlt. Multiple copies of bcr abl gene were uorescence in interphase nuclei imatinib-resistant CML patients with a fl in situ hybridization assay detected. A lot of hours More frequently because of the resistance of the target load are simple amino Ure Ver Changes in Abl kinase Bcr Abl resulting in Bcr-Abl kinase activity of t, but the binding of imatinib to display Community protein. This decrease in Bindungskapazit t can be caused by either direct or indirect mechanisms, whereby classification of Bcr Abl mutations in two groups. Mutations to prevent direct contact between Bcr Abl protein and imatinib: 20 AA are involved in binding imatinib.
Substitution of one of these. May then causes the display community ner reduced imatinib Bcr or Abl the steric inhibition of binding Examples of mutations that are inhibits binding of imatinib those affecting Thr315 and Phe317. The Thr315Ile mutation is clinically important counterpart to Thr670Ile mutation c-kit, PDGFR Thr674Ile viewed in ? ?? ? ?? ? ?? e Thr790Met mutation in EGFR, in the sense that the so-called guardian threonine which is a major determinant for the binding of the inhibitor of the kinase NEN-Dom. Mutations change the r spatial conformation of the protein leads to an indirect loss of imatinib for binding Community display: Nucleotidebinding mutations in the loop and in the activation loop to destabilize available as imatinib can not bind t