Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics

Szu-Yu Kuo, Adam B Castoreno, Leslie N Aldrich, Kara G Lassen, Gautam Goel, Vlado Dančík, Petric Kuballa, Isabel Latorre, Kara L Conway, Sovan Sarkar, Dorothea Maetzel, Rudolf Jaenisch, Paul A Clemons, Stuart L Schreiber, Alykhan F Shamji, Ramnik J Xavier

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)
127 Downloads (Pure)


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 languageEnglish
Pages (from-to)E4281-E4287
JournalNational Academy of Sciences. Proceedings
Issue number31
Publication statusPublished - 4 Aug 2015


  • 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


Dive into the research topics of 'Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics'. Together they form a unique fingerprint.

Cite this