E Lapatinib is an orally bioavailable action thiazolylquinazoline 6 is a potent inhibitor of EGFR and HER-2 is twice. Lapatinib binds to the binding site of adenosine triphosphate both EGFR and HER 2 Lapatinib binds to the inactive form of the EGFR and a slower pace than the dissociation of selective EGFR inhibitors such as erlotinib, which binds to the active TKI258 VEGFR inhibitor form of EGFR. The dissociation constants of beautiful tzungsweise 23 OncoTargets 2008:1 and lapatinib in breast cancer therapy with lapatinib for EGFR and HER-2 were 3.0 ��ԧ� 0.2 and 13 nm ��ԧ� nm are. Lapatinib inhibits EGFR and HER Cleaning ed 2 with a 300-fold selectivity of t compared to other kinases, and IC 50 values of 12 nM. Pr Clinical models have shown that tumor cell lines that express either EGFR or HER-2 more sensitive to lapatinib are.
Rusnak et al, a model to determine the sensitivity of lapatinib in cell lines. The use of a number of human cell lines and normal tumor lay IC50 values ��ԧܧ駲�� 0.025 to 11.5 ��ԧܧ駲��. Sensitivity of the cell line correlates with receptor function, Estrogen Receptor cancer particularly HER-2, although cell lines with EGFR expression and a modest increase in expression also showed her 2-sensitivity. Simultaneous consideration of both receptors was considered the best Pr Predictor for the response. Lapatinib binding of EGFR and HER-2 was shown to reduce EGFR, HER 2, Raf, AKT, MAPK and efficacy. AKT and MAPK his k Can important biomarker of response to lapatinib. MAPK in cell proliferation, and AKT is a critical process in the survival of the cell.
Xia et al reported that lapatinib decreases from F Marked phosphorylation of MAPK and AKT in HER 2-overexpressing breast cancer cell line BT474 and in human tumor xenografts. In vitro corresponded to a 23-fold increase in apoptosis. With gene expression profiles from Hegde et al showed that the results of treatment with lapatinib strong differential regulation of genes in the Akt path-lines in breast cancer cells, compared to less sensitive cell lines. To go Clones whose genes that are involved in the contr The cell cycle and cellular Ren Stoffwechselvorg length. In particular, the lapatinib FOXO3a gene regulates the apoptotic pro-sensitive breast cancer cells lines BT474 and SKBR3. Gene expression profiling also showed that treatment with lapatinib stimulated the expression of hormone receptors in cell lines with estrogen and progesterone moderate.
Interestingly, it has been shown that lapatinib to restore sensitivity to breast cancer in a cell line through the inhibition of estrogen-stimulated Transkriptionsaktivit t tamoxifen. Sun lapatinib may sensitize hormone-refractory to hormonal agents. Pharmacokinetics in six healthy volunteers a single oral dose of 250 mg of lapatinib was the major route of excretion of lapatinib and its metabolites feces. About 20% of the drug excreted unmetabolized. Less than 2% of the excretion in the urine. Pharmacokinetic studies of single and repeated doses of lapatinib in healthy subjects showed a delay Storage in the detection of serum levels of the drug after ingestion, suggesting a delay Storage at the oral intake. Peak serum concentrations occur at a median of three hours. The solubility L Of lapatinib is pH-dependent Dependent and increases with increasing pH. This indicates that the absorption may decrease if the drug through the gastrointestinal tract. It is recommended that lapatinib at least 1 hour be taken before or after a meal. In general, erh Increase in dose led to an increase Increase the serum. Half a drug lif
Related posts:
- Flavopiridol 131740-09-5 open-label, RCT, lapatinib trastuzumab against trastuzumab when compared lapatinib Lapatinib
- Lapatinib HER2 induced cell death within a dose- and time-dependent process
- TW-37 cells expressing wild-type ERBB2 with the EGFR inhibitor erlotinib
- Lapatinib Tykerb effect of the observed antiviral drug cidofovir
- BMS-536924 IGF-1R inhibitor transfected with the EGFRvIII