| pubmed-article:21341675 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21341675 | lifeskim:mentions | umls-concept:C1335204 | lld:lifeskim |
| pubmed-article:21341675 | lifeskim:mentions | umls-concept:C1418440 | lld:lifeskim |
| pubmed-article:21341675 | lifeskim:mentions | umls-concept:C0243077 | lld:lifeskim |
| pubmed-article:21341675 | lifeskim:mentions | umls-concept:C1707689 | lld:lifeskim |
| pubmed-article:21341675 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:21341675 | pubmed:dateCreated | 2011-3-17 | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:abstractText | Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor. | lld:pubmed |
| pubmed-article:21341675 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21341675 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21341675 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21341675 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:21341675 | pubmed:issn | 1520-4804 | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:IpN YNY | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:RabindranSrid... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:BobkoMark AMA | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:MillerWilliam... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:SudakinValery... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:XiangHongH | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:DuquenneCelin... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:BeckerChristo... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:WardParisP | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:DumbleMelissa... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:CampobassoNin... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:RomerilStuart... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:GrantSeth WSW | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:FengYanhongY | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:BlackledgeCha... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:AxtenJeffrey... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:MedinaJesús... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:HeerdingDirkD | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:LiWilliam HWH | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:ScherzerDaryl... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:ShuArthurA | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:ChaddertonAnt... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:GardinerChris... | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:GilbertSethS | lld:pubmed |
| pubmed-article:21341675 | pubmed:author | pubmed-author:BradyPat GPG | lld:pubmed |
| pubmed-article:21341675 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21341675 | pubmed:day | 24 | lld:pubmed |
| pubmed-article:21341675 | pubmed:volume | 54 | lld:pubmed |
| pubmed-article:21341675 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21341675 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21341675 | pubmed:pagination | 1871-95 | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:meshHeading | pubmed-meshheading:21341675... | lld:pubmed |
| pubmed-article:21341675 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21341675 | pubmed:articleTitle | Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors. | lld:pubmed |
| pubmed-article:21341675 | pubmed:affiliation | Oncology Research, GlaxoSmithKline, Collegeville, Pennsylvania 19426, United States. jesus.r.medina@gsk.com | lld:pubmed |
| pubmed-article:21341675 | pubmed:publicationType | Journal Article | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:21341675 | lld:chembl |
