Potent and Selective Inhibition of Acid Sphingomyelinase by Bisphosphonates

More than mending bones: A simple geminal aminobisphosphonate (see picture) is the most potent selective inhibitor of the acid sphingomyelinase known to date. It can be synthesized in a one‐step procedure and inhibits cell death in vitro. Since the acid sphingomyelinase is a putative drug target for...

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Published in:Angewandte Chemie (International ed.) 2009-09, Vol.48 (41), p.7560-7563
Main Authors: Roth, Anke G, Drescher, Daniela, Yang, Yang, Redmer, Susanne, Uhlig, Stefan, Arenz, Christoph
Format: Article
Language:English
Subjects:
Animals
Apoptosis
bioorganic chemistry
bisphosphonates
Cells, Cultured
Diphosphonates - chemical synthesis
Diphosphonates - chemistry
Diphosphonates - metabolism
drug targets
enzyme inhibitors
Female
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Molecular Structure
Rats
Rats, Wistar
sphingolipids
Sphingomyelin Phosphodiesterase - antagonists & inhibitors
Sphingomyelin Phosphodiesterase - metabolism
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Summary:More than mending bones: A simple geminal aminobisphosphonate (see picture) is the most potent selective inhibitor of the acid sphingomyelinase known to date. It can be synthesized in a one‐step procedure and inhibits cell death in vitro. Since the acid sphingomyelinase is a putative drug target for inflammatory lung diseases, bisphosphonates may find application in the treatment of pulmonary diseases.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200903288