| Sign In to gain access to subscriptions and/or personal tools. |
Identification of a Small Molecule That Induces Mitotic Arrest Using a Simplified High-Content Screening Assay and Data Analysis Method
1 Department of Chemical Genomics, ArQule Incorporated, Woburn, MA.
* To whom correspondence should be addressed. E-mail: chris_wilson{at}alum.mit.edu.
High-content screening has emerged as a new and powerful technique for identifying small-molecule modulators of mammalian cell biology. The authors describe the development and execution of a high-content screen to identify small molecules that induce mitotic arrest in mammalian cancer cells. Many widely used chemotherapeutics, such as Taxol® and vinblastine, induce mitotic arrest, and the creation of new drugs that also induce mitotic arrest may have tremendous therapeutic value. In their screen, the authors employed a simple DNA stain (DAPI) and a sensitive nonparametric statistical test to identify compounds from an internal collection of ~13,000 high-quality lead-like small molecules. Subsequent analysis of 1 active compound indicated that it induces mitotic arrest, assessed using a high-content phosphohistone H3 detection assay, and caused cell proliferation defects in multiple cancer cell lines. The active compound, a quinazolinone originating from a natural product-like subset of the screened compounds, is active in cells at ~500 nM and appears to act by inhibiting the polymerization of tubulin. Key Words: high-content screening, image-based screening, mitotic arrest, tubulin
First published on October 18, 2005, doi:10.1177/1087057105280726 This article has been cited by other articles:
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
