an unbiased cell morphology–based screen for new, biologically active small molecules一个无偏细胞morphology-based屏幕为新生物活性小分子.pdfVIP

Open access, freely available online PLoS BIOLOGY An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules 1 1 1 2 2 1 Masahiro Tanaka , Raynard Bateman , Daniel Rauh , Eugeni Vaisberg , Shyam Ramachandani , Chao Zhang , 3 3 2 1* 2 Kirk C. Hansen , Alma L. Burlingame , Jay K. Trautman , Kevan M. Shokat , Cynthia L. Adams 1 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America, 2 Cytokinetics Inc., South San Francisco, California, United States of America, 3 Department of Pharmaceutical Chemistry, Mass Spectrometry Facility, University of California, San Francisco, California, United States of America We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay format provides unbiased analysis of morphological effects induced by small molecules by capturing phenotypic readouts of most known classes of pharmacological agents and has the potential to read out pathways for which little is known. Four human-cancer cell lines and one noncancerous primary cell type were treated with 107 small molecules comprising four different protein kinase–inhibitor scaffolds. Cellular phenotypes induced by each compound were quantified by multivariate statistical analysis of the morphology, staining intensity, and spatial attributes of the cellular nuclei, micr