| pubmed-article:12773051 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12773051 | lifeskim:mentions | umls-concept:C0028027 | lld:lifeskim |
| pubmed-article:12773051 | lifeskim:mentions | umls-concept:C1332322 | lld:lifeskim |
| pubmed-article:12773051 | lifeskim:mentions | umls-concept:C2718002 | lld:lifeskim |
| pubmed-article:12773051 | lifeskim:mentions | umls-concept:C1880355 | lld:lifeskim |
| pubmed-article:12773051 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:12773051 | pubmed:dateCreated | 2003-5-29 | lld:pubmed |
| pubmed-article:12773051 | pubmed:abstractText | By applying a novel cell- and caspase-based HTS assay, a series of N-phenyl nicotinamides has been identified as a new class of potent inducers of apoptosis. Through SAR studies, a 20-fold increase in potency was achieved from a screening hit N-(4-methoxy-2-nitrophenyl)pyridine-3-carboxamide (1) to lead compound 6-methyl-N-(4-ethoxy-2-nitrophenyl)pyridine-3-carboxamide (10), with an EC(50) of 0.082 microM in the caspase activation assay in T47D breast cancer cells. The N-phenyl nicotinamides also were found to be active in the growth inhibition assay where compound 10 had a GI(50) value of 0.21 microM in T47D cells. More importantly, compound 10 was found to be equipotent in MES-SA cells and paclitaxel-resistant, p-glycoprotein overexpressed MES-SA/DX5 cells. Compounds 1 and 6-chloro-N-(4-ethoxy-2-nitrophenyl)pyridine-3-carboxamide (8), a more potent analogue, were found to arrest T47D cells in G(2)/M phase of the cell cycle followed by induction of apoptosis as measured by flow cytometry. Compound 8, which was more potent than 1 in the caspase activation assay, also was found to be more potent in G(2)/M arrest and apoptosis assay. These data confirm that the cell-based caspase activation assay is useful for screening for inducers of apoptosis, as well as for SAR studies and lead optimization. Upon further characterization, N-phenyl nicotinamides were found to be inhibitors of microtubule polymerization in vitro. The identification of N-phenyl nicotinamides as a novel series of inducers of apoptosis demonstrates that our cell- and caspase-based HTS assay is useful for the discovery and optimization of potentially novel anticancer agents. | lld:pubmed |
| pubmed-article:12773051 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12773051 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12773051 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12773051 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:12773051 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:KasibhatlaSha... | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:GuastellaJohn... | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:TsengBenB | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:DreweJohnJ | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:CaiSui... | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:NguyenBaoB | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:JiaShaojuanS | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:HerichJohnJ | lld:pubmed |
| pubmed-article:12773051 | pubmed:author | pubmed-author:ReddySanjeeva... | lld:pubmed |
| pubmed-article:12773051 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12773051 | pubmed:day | 5 | lld:pubmed |
| pubmed-article:12773051 | pubmed:volume | 46 | lld:pubmed |
| pubmed-article:12773051 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12773051 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12773051 | pubmed:pagination | 2474-81 | lld:pubmed |
| pubmed-article:12773051 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:meshHeading | pubmed-meshheading:12773051... | lld:pubmed |
| pubmed-article:12773051 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12773051 | pubmed:articleTitle | Discovery of substituted N-phenyl nicotinamides as potent inducers of apoptosis using a cell- and caspase-based high throughput screening assay. | lld:pubmed |
| pubmed-article:12773051 | pubmed:affiliation | Cytovia, Inc., 6650 Nancy Ridge Drive, San Diego, California 92121, USA. scai@maxim.com | lld:pubmed |
| pubmed-article:12773051 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:12773051 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:12773051 | lld:pubmed |
