Phenotypic screening of small molecule libraries by high throughput cell imaging.
We have developed high throughput fluorescence cell imaging methods to screen chemical libraries for compounds with effects on diverse aspects of cell physiology. We describe screens for compounds that arrest cells in mitosis, that block cell migration, and that block the secretory pathway. Each of these screens yielded specific inhibitors for research use, and the mitosis screen identified Eg5 as a potential target protein for cancer chemotherapy. Cell imaging provides a large amount of information from primary screening data that can be used to distinguish compounds with different effects on cells, and together with automated analysis, to quantitate compound effects.
Yarrow
J C
JC
Institute of Chemistry and Cell biology, Harvard Medical School, Boston, MA 02115, USA.
Feng
Y
Y
Perlman
Z E
ZE
Kirchhausen
T
T
Mitchison
T J
TJ
D000818:Animals; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005057:Eukaryotic Cells / Q000187:drug effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods*; D010641:Phenotype