This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duanmu, C. Articles by Hamel, E. Search for Related Content PubMed PubMed Citation Articles by Duanmu, C. Articles by Hamel, E.

Tubulin-dependent Hydrolysis of Guanosine Triphosphate as a Screening Test to Identify New Antitubulin Compounds with Potential as Antimitotic Agents: Application to Carbamates of Aromatic Amines

Laboratory of Biochemical Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892

Tubulin-dependent GTP hydrolysis was evaluated for its potential as a relatively simple screening assay for new antimitotic drugs. Carbamates of aromatic amines were chosen as the test system because of the relatively diverse structures of compounds in this class already known to have antimitotic properties and because of the large number of such compounds in the NSC collection of the National Cancer Institute. Of 162 compounds evaluated, significant alterations in the GTPase reaction were observed with 26 agents. Sixteen of these had substantial inhibitory effects on tubulin polymerization (true positives), while ten did not (false positives). There were no false negatives (i.e., no agent inactive in the GTPase assay inhibited tubulin polymerization). The true positives were examined for effects on cell growth and mitosis, and four compounds had 50% inhibitory concentration values of 2 µM or less with L1210 murine leukemia cells. All four caused the accumulation of cells in metaphase arrest. We conclude that tubulin-dependent GTP hydrolysis can be used effectively to select new antitubulin compounds with potential as antimitotic agents from a large group of compounds of unknown activity.

¹ To whom requests for reprints should be addressed, at Bldg. 37, Room 5B22, NIH, Bethesda, MD 20892.

Received 7/18/88. Revised 11/ 7/88. Accepted 12/13/88.

This article has been cited by other articles:

				T. Beckers, T. Reissmann, M. Schmidt, A. M. Burger, H. H. Fiebig, U. Vanhoefer, H. Pongratz, H. Hufsky, J. Hockemeyer, M. Frieser, et al. 2-Aroylindoles, a Novel Class of Potent, Orally Active Small Molecule Tubulin Inhibitors Cancer Res., June 1, 2002; 62(11): 3113 - 3119. [Abstract] [Full Text] [PDF]