| pubmed-article:15916429 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0001962 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0033681 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0220781 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C1150423 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C1883254 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0870071 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C0243071 | lld:lifeskim |
| pubmed-article:15916429 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:15916429 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:15916429 | pubmed:dateCreated | 2005-5-26 | lld:pubmed |
| pubmed-article:15916429 | pubmed:abstractText | Utilizing our recently published semisynthetic approach to the (3'S)-K-252a diastereomer, we report the first synthesis of the (3'R)-10 diastereomer and a set of related epimers, with the goal of defining the stereochemical role of the 3'-sugar hydroxyl group on trkA tyrosine kinase activity and selectivity. (3'R)-10 displayed potent trkA inhibitory activity with an IC50 value of 4 nM. The corresponding deshydroxy epimer (3'S)-14 was 7-fold more potent than its 3'R counterpart (natural stereochemistry) with a trkA IC50 value of 3 nM and demonstrated >280-fold selectivity over PKC (IC50 = 850 nM). In cells, (3'S)-14 displayed potent inhibition of trkA autophosphorylation with an IC50 < 10 nM. Molecular modeling studies revealed that the 3'-OH, due to the inverted geometry, forms significant H-bonding interactions with Glu27 and Arg195, an interaction that is not attainable with the natural isomers. | lld:pubmed |
| pubmed-article:15916429 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15916429 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15916429 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15916429 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:15916429 | pubmed:issn | 0022-2623 | lld:pubmed |
| pubmed-article:15916429 | pubmed:author | pubmed-author:AngelesThelma... | lld:pubmed |
| pubmed-article:15916429 | pubmed:author | pubmed-author:HudkinsRobert... | lld:pubmed |
| pubmed-article:15916429 | pubmed:author | pubmed-author:GingrichDiane... | lld:pubmed |
| pubmed-article:15916429 | pubmed:author | pubmed-author:YangShi XSX | lld:pubmed |
| pubmed-article:15916429 | pubmed:author | pubmed-author:GessnerGeorge... | lld:pubmed |
| pubmed-article:15916429 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15916429 | pubmed:day | 2 | lld:pubmed |
| pubmed-article:15916429 | pubmed:volume | 48 | lld:pubmed |
| pubmed-article:15916429 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15916429 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15916429 | pubmed:pagination | 3776-83 | lld:pubmed |
| pubmed-article:15916429 | pubmed:dateRevised | 2011-11-17 | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
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| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:meshHeading | pubmed-meshheading:15916429... | lld:pubmed |
| pubmed-article:15916429 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15916429 | pubmed:articleTitle | Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on trkA tyrosine kinase activity. | lld:pubmed |
| pubmed-article:15916429 | pubmed:affiliation | Department of Medicinal Chemistry, Cephalon, Inc., 145 Brandywine Parkway, West Chester, Pennsylvania 19380, USA. | lld:pubmed |
| pubmed-article:15916429 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:15916429 | lld:chembl |
