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Phenotypic screening in complex cellular extracts to identify novel antimitotic targets and compounds
Author(s) -
King Randall,
Zeng Xing,
Sigoillot Frederic,
Gaur Shantanu,
Choi Sungwoon,
Cuny Gregory
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.464.2
Subject(s) - mitosis , phenotypic screening , small molecule , microbiology and biotechnology , drug discovery , biology , computational biology , xenopus , cell cycle , identification (biology) , high throughput screening , phenotype , anaphase , cell , genetics , bioinformatics , gene , botany
Conventional approaches to drug screening involve identification of a drug target and development of an assay with purified components. In contrast, phenotypic screens in intact cells can identify compounds that act through unique mechanisms, but identifying the targets of active compounds can be challenging. Here I describe our efforts to perform high throughput small molecule screens in complex cellular extracts. This approach harnesses the complexity of cellular systems, yet provides focus that facilitates the process of target identification. We have made use of Xenopus cell cycle extracts to identify small molecules that block cell cycle progression through novel mechanisms. I will describe how these efforts led to the identification of the first small molecule inhibitor of the Anaphase‐Promoting Complex (APC), a ubiquitin ligase required for exit from mitosis. I will discuss why inhibitors of the APC may be more effective at inducing mitotic arrest and cell death than conventional antimitotics that target the mitotic spindle.