| pubmed-article:11259534 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11259534 | lifeskim:mentions | umls-concept:C0024660 | lld:lifeskim |
| pubmed-article:11259534 | lifeskim:mentions | umls-concept:C0456387 | lld:lifeskim |
| pubmed-article:11259534 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:11259534 | lifeskim:mentions | umls-concept:C1880355 | lld:lifeskim |
| pubmed-article:11259534 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:11259534 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:11259534 | pubmed:dateCreated | 2001-3-22 | lld:pubmed |
| pubmed-article:11259534 | pubmed:abstractText | A series of naturally occurring compounds reported recently by multiple laboratories defines a new small-molecule class sharing a unique benzolactone enamide core structure and diverse biological actions, including inhibition of growth of tumor cells and oncogene-transformed cell lines. Here we show that representative members of this class, including salicylihalamide A, lobatamides A-F, and oximidines I and II inhibit mammalian vacuolar-type (H+)-ATPases (V-ATPases) with unprecedented selectivity. Data derived from the NCI 60-cell antitumor screen critically predicted the V-ATPase molecular target, while specific biochemical assays provided confirmation and further illumination. The compounds potently blocked representative V-ATPases from human kidney, liver, and osteoclastic giant-cell tumor of bone but were essentially inactive against V-ATPases of Neurospora crassa and Saccharomyces cerevisiae and other membrane ATPases. Essential regulation of pH in cytoplasmic, intraorganellar, and local extracellular spaces is provided by V-ATPases, which are ubiquitously distributed among eukaryotic cells and tissues. The most potent and selective V-ATPase inhibitors heretofore known were the bafilomycins and concanamycins, which do not discriminate between mammalian and nonmammalian V-ATPases. Numerous physiological processes are mediated by V-ATPases, and aberrant V-ATPase functions are implicated in many different human diseases. Previous efforts to develop therapeutic pharmacological modulators of V-ATPases have been frustrated by a lack of synthetically tractable and biologically selective leads. Therefore, availability of the unique benzolactone enamide inhibitor class may enable further elucidation of functional and architectural features of mammalian versus nonmammalian V-ATPase isoforms and provide new opportunities for targeting V-ATPase-mediated processes implicated in diverse pathophysiological phenomena, including cancer. | lld:pubmed |
| pubmed-article:11259534 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259534 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259534 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11259534 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259534 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11259534 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11259534 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259534 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11259534 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:11259534 | pubmed:issn | 0022-3565 | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:BoydM RMR | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:BowmanB JBJ | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:HayakawaYY | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:BowmanE JEJ | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:KimJ WJW | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:BeutlerJ AJA | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:GagliardiSS | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:FarinaCC | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:BelfiorePP | lld:pubmed |
| pubmed-article:11259534 | pubmed:author | pubmed-author:McKeeT CTC | lld:pubmed |
| pubmed-article:11259534 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11259534 | pubmed:volume | 297 | lld:pubmed |
| pubmed-article:11259534 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11259534 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11259534 | pubmed:pagination | 114-20 | lld:pubmed |
| pubmed-article:11259534 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:11259534 | pubmed:meshHeading | pubmed-meshheading:11259534... | lld:pubmed |
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| pubmed-article:11259534 | pubmed:meshHeading | pubmed-meshheading:11259534... | lld:pubmed |
| pubmed-article:11259534 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11259534 | pubmed:articleTitle | Discovery of a novel antitumor benzolactone enamide class that selectively inhibits mammalian vacuolar-type (H+)-atpases. | lld:pubmed |
| pubmed-article:11259534 | pubmed:affiliation | Laboratory of Natural Products, Division of Basic Sciences, National Cancer Institute, Bldg. 1052, Rm. 121, Frederick, MD 21702-1201, USA. boyd@tdpax2.ncifcrf.gov | lld:pubmed |
| pubmed-article:11259534 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11259534 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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