W Re Kinaseaktivit t Page Moasser t Oncogene inhibit Author manuscript eighth PMC 2011 on 6 April. ATP-binding pocket in the catalytic Cathedral. Some of these compounds bind reversibly to the ATP pocket and SB-207499 phosphodiesterase(pde) compete with ATP bind w W While other irreversible and are not in competition with ATP. Although his family kinases are highly homologous, TKI, many t selectivity t among the family members, if they. By in vitro kinase assays using purified EGFR, HER2 or HER4 kinases are examined, and these are listed in Table 2 Not the biological relevance of these in vitro properties in cellular Assays Ren obviously. Gefitinib inhibits the selective phosphorylation of EGFR in the cells of the entire protein HER, as well as the selective agent HER2 654 577 CP.
In cell proliferation assays HER2 tumors are particularly sensitive to the 659th EGFR TKI gefitinib very selective, AG1478, CGP 59326A and EKB are overexpressing tumors in fact, an engineering model of HER2, the degree of HER2 overexpression correlates directly sensitivity to EGFR TKI AG1478 selectively. The mechanisms by which the EGFR TKI activity of WZ4002 t Selective for HER2 e HER2 signaling and growth-oriented currently not understood and can occur through direct inhibition of HER2 kinase by sw high monitoring their activity t HER2 exclusion TS Re intracellular Higher concentrations of these agents or their first goals of the selectivity t ben for EGFR HER2 growth CONFIRMS is born. This seems unlikely, at least since fibroblasts models, transformed and in the absence of EGFR-expressing HER2.
These uncertainties about the biological significance of some targetspecificity are theoretically and practically every show TKI activity T T HER2 tumors in mouse models, what their target selectivity t Th concentrations in vitro, and they are all potential candidates for agents are the assumptions patients overexpressed HER2 treatment with HER2 cancers. Clinical anti-tumor activity of t T many ITK its current data are in various stages of clinical development and clinical pr. The clinical development of each of these sub-types is a priority Tt For authors certain cancers, so the activity of t TH against cancer HER2 engine not in its infancy tested k Can K. But a limited number of clinical data is now ready for a first impression of the antitumor efficacy of this class of TKIs in patients with HER2 overexpressing cancer type available.
Data currently reported phase II study in combination efficacy in Table 3 Zus tzlich forums many multi-TKI drugs targeting kinases there Target families tzlich longer its other family kinases in the development and clinical called pr, although these drugs can k born Active than K in the treatment of cancer HER2 inputted targeting multiple properties. less able to support the hypothesis that the oncogenic HER2 test II study of gefitinib and erlotinib in patients with breast cancer reported phase support. Although it is not specifically in patients with HER2 overexpressing cancer conducted cohorts to other patients with HER2-positive disease. The overall response rate of 0 10% were observed in the first