Abstract：
:Phenotype-based small-molecule screening is a powerful method to identify molecules that regulate cellular functions. However, such screens are generally performed in vitro under conditions that do not necessarily model complex physiological conditions or disease states. Here, we use molecular cell barcoding to enable direct in vivo phenotypic screening of small-molecule libraries. The multiplexed nature of this approach allows rapid in vivo analysis of hundreds to thousands of compounds. Using this platform, we screened >700 covalent inhibitors directed toward hydrolases for their effect on pancreatic cancer metastatic seeding. We identified multiple hits and confirmed the relevant target of one compound as the lipase ABHD6. Pharmacological and genetic studies confirmed the role of this enzyme as a regulator of metastatic fitness. Our results highlight the applicability of this multiplexed screening platform for investigating complex processes in vivo.
journal_name
Nat Methodsjournal_title
Nature methodsauthors
Grüner BM,Schulze CJ,Yang D,Ogasawara D,Dix MM,Rogers ZN,Chuang CH,McFarland CD,Chiou SH,Brown JM,Cravatt BF,Bogyo M,Winslow MMdoi
10.1038/nmeth.3992subject
Has Abstractpub_date
2016-10-01 00:00:00pages
883-889issue
10eissn
1548-7091issn
1548-7105journal_volume
13pub_type
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