Abstract:
:The receptor tyrosine kinases (for example EGFR, PDGFR, VEGFR) are a transmembrane protein family which plays a crucial role in tumor growth, survival, metastasis dissemination and angiogenesis. During the past 10 years, many tyrosine kinase inhibitors (TKIs) have been approved for cancer treatment (imatinib, gefitinib, erlotinib, sunitinib, sorafenib). These compounds generally possess a pyrrolo- or pyrimido- pyrimidine scaffold or approaching molecular structure. We synthesized 10 thienopyrimidine compounds (including 5 newly synthesized) whose scaffold is very similar to the agents cited above. The cytotoxicity of these agents was evaluated using a MTT assay and a flow cytometry technique on glioblastoma cell lines. Two compounds showed a similar cytotoxicity to the standard anti-EGFR gefitinib (IC50: gefitinib=51.9 microM, 6b=61.8 microM, 6c=41.2 microM), suggesting a blockade of the EGFR pathway by binding to the TK receptor.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Pédeboscq S,Gravier D,Casadebaig F,Hou G,Gissot A,De Giorgi F,Ichas F,Cambar J,Pometan JPdoi
10.1016/j.ejmech.2010.02.032subject
Has Abstractpub_date
2010-06-01 00:00:00pages
2473-9issue
6eissn
0223-5234issn
1768-3254pii
S0223-5234(10)00149-2journal_volume
45pub_type
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