DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Hwangseo | ko |
dc.contributor.author | Lee, Soyoung | ko |
dc.contributor.author | Hong, Sungwoo | ko |
dc.date.accessioned | 2013-03-12T21:25:30Z | - |
dc.date.available | 2013-03-12T21:25:30Z | - |
dc.date.created | 2012-08-22 | - |
dc.date.created | 2012-08-22 | - |
dc.date.issued | 2012-08 | - |
dc.identifier.citation | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.22, no.15, pp.4946 - 4950 | - |
dc.identifier.issn | 0960-894X | - |
dc.identifier.uri | http://hdl.handle.net/10203/103565 | - |
dc.description.abstract | Mitogen/extracellular signal-regulated kinase (MEK) and phosphoinositide 3-kinase (PI3K alpha) are considered to be promising targets for the development of anticancer therapeutics. We report the first example of the successful application of structure-based virtual screening to identify novel inhibitors of MEK with IC50 values ranging from 1 to 25 mu M. One of the four newly identified MEK inhibitors was found to be also a potent inhibitor of PI3K alpha with submicromolar inhibitory activity (IC50 = 0.3 mu M). Because this dual inhibitor was screened for having desirable physicochemical properties as a drug candidate as well as the high inhibitory activities against MEK and PI3K alpha, it warrants further development through structure-activity relationship (SAR) studies to optimize the inhibitory and anticancer activities. Structural features relevant to the stabilization of the dual inhibitor in the ATP-binding sites of MEK1 and PI3K alpha are addressed in detail. (c) 2012 Elsevier Ltd. All rights reserved. | - |
dc.language | English | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.subject | SMALL-MOLECULE INHIBITORS | - |
dc.subject | PROTEIN-KINASE CASCADE | - |
dc.subject | CRYSTAL-STRUCTURES | - |
dc.subject | GENETIC ALGORITHM | - |
dc.subject | CANCER | - |
dc.subject | SOLVATION | - |
dc.subject | DOCKING | - |
dc.subject | DOMAIN | - |
dc.subject | IDENTIFICATION | - |
dc.subject | MUTATION | - |
dc.title | Discovery of MEK/PI3K dual inhibitor via structure-based virtual screening | - |
dc.type | Article | - |
dc.identifier.wosid | 000306481100006 | - |
dc.identifier.scopusid | 2-s2.0-84863986613 | - |
dc.type.rims | ART | - |
dc.citation.volume | 22 | - |
dc.citation.issue | 15 | - |
dc.citation.beginningpage | 4946 | - |
dc.citation.endingpage | 4950 | - |
dc.citation.publicationname | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | - |
dc.identifier.doi | 10.1016/j.bmcl.2012.06.041 | - |
dc.contributor.localauthor | Hong, Sungwoo | - |
dc.contributor.nonIdAuthor | Park, Hwangseo | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Anticancer | - |
dc.subject.keywordAuthor | Virtual screening | - |
dc.subject.keywordAuthor | Drug discovery | - |
dc.subject.keywordAuthor | Docking | - |
dc.subject.keywordAuthor | MEK-PI3K dual inhibitor | - |
dc.subject.keywordPlus | SMALL-MOLECULE INHIBITORS | - |
dc.subject.keywordPlus | PROTEIN-KINASE CASCADE | - |
dc.subject.keywordPlus | CRYSTAL-STRUCTURES | - |
dc.subject.keywordPlus | GENETIC ALGORITHM | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | SOLVATION | - |
dc.subject.keywordPlus | DOCKING | - |
dc.subject.keywordPlus | DOMAIN | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | MUTATION | - |
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