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http://dx.doi.org/10.5012/bkcs.2012.33.5.1571

Design and Synthesis of an Anticancer Diarylurea Derivative with Multiple-Kinase Inhibitory Effect  

El-Gamal, Mohammed I. (Center for Biomaterials, Korea Institute of Science and Technology)
Oh, Chang-Hyun (Center for Biomaterials, Korea Institute of Science and Technology)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.5, 2012 , pp. 1571-1576 More about this Journal
Abstract
A diarylurea compound 1 possessing pyrrolo[3,2-$c$]pyridine nucleus was designed and synthesized with structure similarity to Sorafenib. Compound 1 was tested over 60-cancer cell line panel at a single dose concentration of 10 ${\mu}M$ and showed high activity. It was further tested in a five-dose mode to determine its $IC_{50}$, TGI, and $LC_{50}$ values over the 60 cell lines. Compound 1 showed high potency and good efficacy, and was accordingly tested at a single dose concentration of 10 ${\mu}M$ over a panel of 40 kinases. At this concentration, it completely inhibited the enzymatic activities of a number of oncogenic kinases, including ABL, ALK, c-RAF, FLT3, KDR, and TrkB. The target compound was subsequently tested over these 6 kinases in 10-dose testing mode in order to determine its $IC_{50}$ values.
Keywords
Anticancer; Diarylurea; Multiple-kinase; Pyrrolo[3; 2-$c$]pyridine;
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