Abstract:
:The non-receptor Src tyrosine kinase is known to cooperate with the epidermal growth factor receptor in a mechanism leading to invasion and metastasis of solid tumours. With the purpose of developing agents targeted to both epidermal growth factor receptor and Src or related kinases, we embarked on the design of chimeric molecules termed combi-molecules capable of blocking both Src and epidermal growth factor receptor. To this end, we have chosen to design molecules containing a quinazoline moiety (directed at epidermal growth factor receptor) and a 7-phenyl-pyrazolopyrimidine (directed at Src). Molecular modelling showed that the optimal position to attach the linker was the 6-position of the quinazoline and the 9-position of the pyrazolopyrimidine. This has led to the synthesis of SB162, SB166 and SB163. SB163 containing the longest linker was the only molecule capable of inducing a dose-dependent inhibition of both Src and epidermal growth factor receptor. SB163 also induced a dose inhibition of Abl and PDGFR.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Barchéchath S,Williams C,Saade K,Lauwagie S,Jean-Claude Bdoi
10.1111/j.1747-0285.2009.00786.xsubject
Has Abstractpub_date
2009-04-01 00:00:00pages
380-7issue
4eissn
1747-0277issn
1747-0285pii
JPP786journal_volume
73pub_type
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