Full metadata record

DC FieldValueLanguage
dc.contributor.author노은주-
dc.contributor.author백소라-
dc.contributor.author아흐메드 엘캄하위-
dc.contributor.author아흐메드 하산-
dc.contributor.author이용섭-
dc.date.accessioned2021-06-09T04:18:55Z-
dc.date.available2021-06-09T04:18:55Z-
dc.date.issued2017-12-
dc.identifier.citationVOL 75-405-
dc.identifier.issn0045-2068-
dc.identifier.other49710-
dc.identifier.urihttp://pubs.kist.re.kr/handle/201004/66588-
dc.description.abstractSearching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC50 1.05&#8211-
dc.description.abstract5.37&#8239-
dc.description.abstractμM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands.-
dc.publisherBioorganic chemistry-
dc.subjectAntiproliferative hits-
dc.subjectEGFR inhibitors-
dc.subjectPhenotypic screening-
dc.subjectAnticancer cell lines assay-
dc.subjectPyrimidine derivatives-
dc.titleHit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library-
dc.typeArticle-
dc.relation.page393405-
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE