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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-3-2
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pubmed:abstractText |
A series of 3-aroyl indazoles was synthesized. Modification of the C-7 position resulted in a significant structure-activity relationship (SAR) with acetylene modifications conferring unusual potency in a tumor cell cytotoxicity assay. The most potent compounds exceeded the activity of combretastatin A4 (CA-4), showing single digit nM IC50 values against all cell lines tested including those with known efflux resistance pumps. The inhibition of in vitro tubulin polymerization was comparable to CA-4, consistent with tubulin being the target for these compounds. Competition binding experiments employing [3H]colchicine and purified tubulins demonstrated that the compound specifically binds to the colchicine site.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1001-6
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pubmed:meshHeading |
pubmed-meshheading:17286393-Acetylene,
pubmed-meshheading:17286393-Animals,
pubmed-meshheading:17286393-Binding, Competitive,
pubmed-meshheading:17286393-Binding Sites,
pubmed-meshheading:17286393-Cattle,
pubmed-meshheading:17286393-Cell Line, Tumor,
pubmed-meshheading:17286393-Colchicine,
pubmed-meshheading:17286393-Drug Resistance, Neoplasm,
pubmed-meshheading:17286393-Drug Screening Assays, Antitumor,
pubmed-meshheading:17286393-Humans,
pubmed-meshheading:17286393-Indazoles,
pubmed-meshheading:17286393-Radioligand Assay,
pubmed-meshheading:17286393-Stilbenes,
pubmed-meshheading:17286393-Structure-Activity Relationship,
pubmed-meshheading:17286393-Tubulin,
pubmed-meshheading:17286393-Tubulin Modulators
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pubmed:year |
2007
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pubmed:articleTitle |
Potent antitubulin tumor cell cytotoxins based on 3-aroyl indazoles.
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pubmed:affiliation |
Threshold Pharmaceuticals, 1300 Seaport Boulevard, Redwood City, California 94063, USA. jduan@thresholdpharm.com
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pubmed:publicationType |
Journal Article
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