Journal
ORGANIC LETTERS
Volume 20, Issue 18, Pages 5529-5532Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.8b01871
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Funding
- University of Wisconsin-Madison School of Pharmacy
- NIH through the administration of NIGMS [R01GM104192]
- University of Wisconsin Carbone Cancer Center Support Grant [P30 CA014520]
- NIH [P41GM103399]
- NATIONAL CANCER INSTITUTE [P30CA014520] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM104192, P41GM103399] Funding Source: NIH RePORTER
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Screening of a marine natural products library for inhibitors of TGF/beta revealed five pyrimidinedione derivatives, biemamides A-E (1-5). The structures were determined by 2D NMR and HRMS experiments; absolute configurations were established by advanced Marfey's analysis and ECD calculations. Biemamides A-E specifically inhibited in vitro TGF-beta induced epithelial to mesenchymal transition in NMuMG cells. Additionally, using Caenorhabditis elegans, selected biemmamides were found to influence in vivo developmental processes related to body size regulation in a dose-dependent manner.
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