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

Burns, Christopher J., Fantino, Emmanuelle, Phillips, Ian D., Su, Stephen, Harte, Michael F., Bukczynska, Patricia E., Frazzetto, Mark, Joffe, Max, Kruszelnicki, Irma, Wang, Bing, Wang, Yue, Wilson, Neil, Dilley, Rodney J., Wan, Soo S., Charman, Susan A., Shackleford, David M., Fida, Rosa, Malcontenti-Wilson, Cathy and Wilks, Andrew F. (2009) CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo. Molecular Cancer Therapeutics, 8 11: 3036-3045. doi:10.1158/1535-7163.MCT-09-0076


Author Burns, Christopher J.
Fantino, Emmanuelle
Phillips, Ian D.
Su, Stephen
Harte, Michael F.
Bukczynska, Patricia E.
Frazzetto, Mark
Joffe, Max
Kruszelnicki, Irma
Wang, Bing
Wang, Yue
Wilson, Neil
Dilley, Rodney J.
Wan, Soo S.
Charman, Susan A.
Shackleford, David M.
Fida, Rosa
Malcontenti-Wilson, Cathy
Wilks, Andrew F.
Title CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo
Journal name Molecular Cancer Therapeutics   Check publisher's open access policy
ISSN 1535-7163
Publication date 2009-11-01
Sub-type Article (original research)
DOI 10.1158/1535-7163.MCT-09-0076
Volume 8
Issue 11
Start page 3036
End page 3045
Total pages 10
Place of publication United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
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 Bcl-2, along with increased expression of cyclin B1. Caspase-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 pharmacologic and pharmacokinetic properties and has considerable potential as a novel anticancer agent.
Keyword Anticancer Drugs
Agents
Microtubules
Target
Apoptosis
Cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Medicine Publications
 
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