CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo

Christopher Burns, Emmanuelle Fantino, Ian D Phillips, Stephen Su, Michael Harte, Patricia Evelina Bukczynska, Mark Frazzetto, Max Joffe, Irma Kruszelnicki, Bing Wang, Yue Wang, Neil Wilson, Rodney James Dilley, Soo S Wan, Susan Ann Charman, David Shackleford, Rosa Fida, Cathy Malcontenti-Wilson, Andrew Frederick Wilks

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25 Citations (Scopus)


CYT997 is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 blocks the cell cycle at the G2 _M boundary, and Western blot analysis indicates an increase in phosphorylated BcI-2, along with increased expression of cyclin B1. Capsase-3 activation is also observed in cells treated with CYT997 along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 possesses a useful combination of pharmacological potential as a novel anticancer agent.
Original languageEnglish
Pages (from-to)3036 - 3045
Number of pages10
JournalMolecular Cancer Therapeutics
Issue number11
Publication statusPublished - 2009

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