Src Kinase Inhibitors as Anticancer Agents
Posted October 19, 2009
Src is a tyrosine kinase that transmits signals from upstream proteins—such as G protein-coupled receptors, growth factor receptors, and tyrosine kinase receptors—to downstream proteins by phosphorylating them on tyrosine residues. Ultimately, Src activation causes increased angiogenesis and cell invasiveness. Src is upregulated in 70% of colon cancers, 60% of breast cancers, and 90% of pancreatic cancers.
Kim Arndt, director in oncology at Wyeth Research, and colleagues screened 1700 synthesized compounds to identify those that best inhibit Src kinase. Arndt focused his talk on Src Kinase Inhibitor, compound 606 (SKI-606). SKI-606 inhibits Src in cells at a 100 nanomolar concentration, which is within the practical dosing range for humans. Analogs of SKI-606 and SKI-606 itself were further evaluated for specificity, ability to inhibit anchorage-dependent growth in culture, and inhibition of tumor growth in mice.
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Kim Timothy Arndt, PhD
Kim Timothy Arndt is director of oncology at Wyeth Research in Pearl River, NY. He joined Wyeth at the end of 1996 first as a principal scientist and then as associate director from 2000 to the end of 2003. Before Wyeth, Arndt was senior staff investigator at Cold Spring Harbor Laboratory from 1988 to 1996.
Arndt completed a postdoctoral fellowship at the Whitehead Institute for Biomedical Research with Gerald Fink from 1984 to 1988. He held a prior postdoctoral position from 1982 to 1984 at the University of Pennsylvania under Stan Opella. He also earned his PhD at the University of Pennsylvania.
Anjani Shah is a freelance science and medical writer based in New York City with a PhD in cell biology.