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Mol Cancer Ther. 2006;5:450-456
© 2006 American Association for Cancer Research

A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities

Pui-Kai Li1, Bulbul Pandit1, Dan L. Sackett2, Zhigen Hu1, Jennifer Zink1, Jiandong Zhi1, Dena Freeman1, Robert W. Robey3, Karl Werbovetz1, Andrew Lewis1 and Chenglong Li1

1 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio and 2 Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development; 3 National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Pui-Kai Li, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 338 Parks Hall, 500 West 12th Avenue, Columbus, OH 43210-1291. Phone: 614-688-0253; Fax: 614-688-8556. E-mail: li.27{at}osu.edu

We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent. [Mol Cancer Ther 2006;5(2):450–6]

Grant support: Intramural Research Program of National Institute of Child Health and Human Development, NIH.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

4 H. XU, unpublished data.

Received 7/26/05; revised 11/ 1/05; accepted 12/16/05.




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[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the American Association for Cancer Research.