A systematic approach to therapeutic target selection in oesophago-gastric cancer was written by Paterson, Anna L.;Shannon, Nicholas B.;Lao-Sirieix, Pierre;Ong, Chin-Ann J.;Peters, Christopher J.;O’Donovan, Maria;Fitzgerald, Rebecca C.. And the article was included in Gut in 2013.Application of 219580-11-7 The following contents are mentioned in the article:
Objective The success of personalised therapy depends on identification and inhibition of the oncogene(s) on which that tumor is dependent. We aimed to determine whether a receptor tyrosine kinase (RTK) array could be used to select the most effective therapeutic strategies in molecularly heterogeneous oesophago-gastric adenocarcinomas. Design Gene expression profiling from oesophagogastric tumors (n = 75) and preinvasive stages (n = 57) identified the active signalling pathways, which was confirmed using immunohistochem. (n = 434). RTK arrays on a cell line panel (n = 14) determined therapeutic targets for in vitro cytotoxic testing. Feasibility of this personalised approach was tested in tumor samples (n = 46). Results MAPK was the most frequently activated pathway (32/75 samples (42.7%)) with progressive enrichment in preinvasive disease stages (p<0.05) and ERK phosphorylation in 148/434 (34.3%) independent samples. Cell lines displayed a range of RTK activation profiles. When no RTKs were activated, tyrosine kinase inhibitors (TKIs) and a Mek inhibitor were not useful (MKN1). In lines with a dominant phosphorylated RTK (OE19, MKN45 and KATOIII), selection of this TKI or Mek in nM concentrations induced cytotoxicity and inhibited Erk and Akt phosphorylation. In cells lines with complex activation profiles (HSC39 and OE33), a combination of TKIs or Mek inhibition (in nM concentrations) was necessary for cytotoxicity and inhibition of Erk and Akt phosphorylation. Human tumors demonstrated diverse activation profiles and 65% of cases had two or more active RTKs. Conclusions The MAPK pathway is commonly activated in oesophago-gastric cancer following activation of a variety of RTKs. Mol. phenotyping can inform a rational choice of targeted therapy. This study involved multiple reactions and reactants, such as 1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7Application of 219580-11-7).
1-(tert-Butyl)-3-(2-((4-(diethylamino)butyl)amino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)urea (cas: 219580-11-7) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. As nucleotides in DNA and RNA, pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Application of 219580-11-7
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia