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  A class of diacylglycerol acyltransferase 1 inhibitors identified by a combination of phenotypic high-throughput screening, genomics, and genetics.

Tschapalda, K., Zhang, Y. Q., Liu, L., Golovnina, K., Schlemper, T., Eichmann, T. O., et al. (2016). A class of diacylglycerol acyltransferase 1 inhibitors identified by a combination of phenotypic high-throughput screening, genomics, and genetics. EBioMedicine, 8, 49-59. doi:10.1016/j.ebiom.2016.04.014.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-0E2A-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-267A-7
Genre: Journal Article

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 Creators:
Tschapalda, K.1, Author              
Zhang, Y. Q, Author
Liu, L., Author
Golovnina, K., Author
Schlemper, T., Author
Eichmann, T. O., Author
Lal-Nag, M., Author
Sreenivasan, U., Author
McLenithan, J., Author
Ziegler, S., Author
Sztalryd, C., Author
Lass, A., Author
Auld, D., Author
Oliver, B., Author
Waldmann, H., Author
Li, Z., Author
Shen, M., Author
Boxer, M. B., Author
Beller, M., Author
Affiliations:
1Department of Molecular Developmental Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_578590              

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 Abstract: Excess lipid storage is an epidemic problemin human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human) and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.

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Language(s): eng - English
 Dates: 2016-04-162016-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.ebiom.2016.04.014
 Degree: -

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Title: EBioMedicine
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 8 Sequence Number: - Start / End Page: 49 - 59 Identifier: -