Abstract
Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.
Original language | English |
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Pages (from-to) | E4281-E4287 |
Journal | National Academy of Sciences. Proceedings |
Volume | 112 |
Issue number | 31 |
DOIs | |
Publication status | Published - 4 Aug 2015 |
Keywords
- Autophagy
- Bacteria
- Carrier Proteins
- Cell Aggregation
- Genetics, Medical
- Green Fluorescent Proteins
- HeLa Cells
- High-Throughput Screening Assays
- Humans
- Induced Pluripotent Stem Cells
- Interleukin-1beta
- Membrane Glycoproteins
- Models, Biological
- Neurons
- Niemann-Pick Disease, Type C
- Peptides
- Phenotype
- Small Molecule Libraries