| pubmed-article:20684549 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C0226896 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C0205531 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C0442027 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C1527415 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C0935763 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C1880355 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C1879762 | lld:lifeskim |
| pubmed-article:20684549 | lifeskim:mentions | umls-concept:C0070966 | lld:lifeskim |
| pubmed-article:20684549 | pubmed:issue | 17 | lld:pubmed |
| pubmed-article:20684549 | pubmed:dateCreated | 2010-9-2 | lld:pubmed |
| pubmed-article:20684549 | pubmed:abstractText | The discovery of aurora kinases as essential regulators of cell division has led to intense interest in identifying small molecule aurora kinase inhibitors for the potential treatment of cancer. A high-throughput screening effort identified pyridinyl-pyrimidine 6a as a moderately potent dual inhibitor of aurora kinases -A and -B. Optimization of this hit resulted in an anthranilamide lead (6j) that possessed improved enzyme and cellular activity and exhibited a high level of kinase selectivity. However, this anthranilamide and subsequent analogues suffered from a lack of oral bioavailability. Converting the internally hydrogen-bonded six-membered pseudo-ring of the anthranilamide to a phthalazine (8a-b) led to a dramatic improvement in oral bioavailability (38-61%F) while maintaining the potency and selectivity characteristics of the anthranilamide series. In a COLO 205 tumor pharmacodynamic assay measuring phosphorylation of the aurora-B substrate histone H3 at serine 10 (p-histone H3), oral administration of 8b at 50 mg/kg demonstrated significant reduction in tumor p-histone H3 for at least 6 h. | lld:pubmed |
| pubmed-article:20684549 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:20684549 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:20684549 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20684549 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20684549 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:20684549 | pubmed:issn | 1520-4804 | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:TangJinJ | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:HuangXinX | lld:pubmed |
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| pubmed-article:20684549 | pubmed:author | pubmed-author:SunJi-RongJR | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:GuYanY | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:RadinskyRober... | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:CeeVictor JVJ | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:KendallRichar... | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:ChungGraceG | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:ZhaoHuilinH | lld:pubmed |
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| pubmed-article:20684549 | pubmed:author | pubmed-author:ChengAlan CAC | lld:pubmed |
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| pubmed-article:20684549 | pubmed:author | pubmed-author:BeXuhaiX | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:NguyenHanh... | lld:pubmed |
| pubmed-article:20684549 | pubmed:author | pubmed-author:EdenPatrick... | lld:pubmed |
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| pubmed-article:20684549 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20684549 | pubmed:day | 9 | lld:pubmed |
| pubmed-article:20684549 | pubmed:volume | 53 | lld:pubmed |
| pubmed-article:20684549 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20684549 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20684549 | pubmed:pagination | 6368-77 | lld:pubmed |
| pubmed-article:20684549 | pubmed:dateRevised | 2011-7-11 | lld:pubmed |
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| pubmed-article:20684549 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20684549 | pubmed:articleTitle | Discovery of a potent, selective, and orally bioavailable pyridinyl-pyrimidine phthalazine aurora kinase inhibitor. | lld:pubmed |
| pubmed-article:20684549 | pubmed:affiliation | Department of Medicinal Chemistry, Amgen Inc., 360 Binney Street, Cambridge, Massachusetts 02142 and Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. vcee@amgen.com | lld:pubmed |
| pubmed-article:20684549 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20684549 | pubmed:publicationType | In Vitro | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:20684549 | lld:chembl |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20684549 | lld:pubmed |
