
Chemical Inhibitors of a Selective SWI/SNF Function Synergize with ATR Inhibition in Cancer Cell Killing.
SWI/SNF (BAF) complexes are a diverse family of ATP-dependent chromatin remodelers produced by combinatorial assembly that are mutated in and thought to contribute to 20% of human cancers and a large number of neurologic diseases. The gene-activating functions of BAF complexes are essential for viability of many cell types, limiting the development of small molecule inhibitors. To circumvent the potential toxicity of SWI/SNF inhibition, we identified small molecules that inhibit the specific repressive function of these complexes but are relatively nontoxic and importantly synergize with ATR inhibitors in killing cancer cells. Our studies suggest an avenue for therapeutic enhancement of ATR/ATM inhibition and provide evidence for chemical synthetic lethality of BAF complexes as a therapeutic strategy in cancer.
Duke Scholars
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Related Subject Headings
- Transcription Factors
- Protein Kinase Inhibitors
- Organic Chemistry
- Neoplasms
- Humans
- HCT116 Cells
- Chromatin Assembly and Disassembly
- Cell Cycle
- Ataxia Telangiectasia Mutated Proteins
- 34 Chemical sciences
Citation

Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Transcription Factors
- Protein Kinase Inhibitors
- Organic Chemistry
- Neoplasms
- Humans
- HCT116 Cells
- Chromatin Assembly and Disassembly
- Cell Cycle
- Ataxia Telangiectasia Mutated Proteins
- 34 Chemical sciences