| Literature DB >> 26195741 |
Szu-Yu Kuo1, Adam B Castoreno2, Leslie N Aldrich3, Kara G Lassen4, Gautam Goel5, Vlado Dančík2, Petric Kuballa5, Isabel Latorre2, Kara L Conway4, Sovan Sarkar6, Dorothea Maetzel7, Rudolf Jaenisch8, Paul A Clemons2, Stuart L Schreiber9, Alykhan F Shamji10, Ramnik J Xavier11.
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.Entities:
Keywords: Crohn’s disease; autophagy; high-throughput screening; small-molecule probes
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Year: 2015 PMID： 26195741 PMCID： PMC4534235 DOI： 10.1073/pnas.1512289112
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205