|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
2003-12-31
|
|
pubmed:abstractText |
Gastropod mollusks have been used for over 2500 years to produce the "Tyrian purple" dye made famous by the Phoenicians. This dye is constituted of mixed bromine-substituted indigo and indirubin isomers. Among these, the new natural product 6-bromoindirubin and its synthetic, cell-permeable derivative, 6-bromoindirubin-3'-oxime (BIO), display remarkable selective inhibition of glycogen synthase kinase-3 (GSK-3). Cocrystal structure of GSK-3beta/BIO and CDK5/p25/indirubin-3'-oxime were resolved, providing a detailed view of indirubins' interactions within the ATP binding pocket of these kinases. BIO but not 1-methyl-BIO, its kinase inactive analog, also inhibited the phosphorylation on Tyr276/216, a GSK-3alpha/beta activation site. BIO but not 1-methyl-BIO reduced beta-catenin phosphorylation on a GSK-3-specific site in cellular models. BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3.
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
1074-5521
|
|
pubmed:author |
pubmed-author:BrivanlouAliA,
pubmed-author:CrovaceClaudiaC,
pubmed-author:DajaniRanaR,
pubmed-author:GreengardPaulP,
pubmed-author:KnockaertMarieM,
pubmed-author:LeostMaryseM,
pubmed-author:MagiatisProkopiosP,
pubmed-author:MeijerLaurentL,
pubmed-author:MusacchioAndreaA,
pubmed-author:PearlLaurenceL,
pubmed-author:PolychronopoulosPanagiotisP,
pubmed-author:RoeS MarkSM,
pubmed-author:RyanXiaozhou PXP,
pubmed-author:SkaltsounisAlexios-LeandrosAL,
pubmed-author:TarriconeCataldoC,
pubmed-author:VonicaClaudia AlinCA
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
10
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1255-66
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:14700633-Animals,
pubmed-meshheading:14700633-Binding Sites,
pubmed-meshheading:14700633-Cell Line,
pubmed-meshheading:14700633-Crystallography, X-Ray,
pubmed-meshheading:14700633-Embryo, Nonmammalian,
pubmed-meshheading:14700633-Enzyme Inhibitors,
pubmed-meshheading:14700633-Glycogen Synthase Kinase 3,
pubmed-meshheading:14700633-Indoles,
pubmed-meshheading:14700633-Models, Molecular,
pubmed-meshheading:14700633-Molecular Structure,
pubmed-meshheading:14700633-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:14700633-Protein Structure, Tertiary,
pubmed-meshheading:14700633-Proto-Oncogene Proteins,
pubmed-meshheading:14700633-Shellfish,
pubmed-meshheading:14700633-Signal Transduction,
pubmed-meshheading:14700633-Substrate Specificity,
pubmed-meshheading:14700633-Wnt Proteins,
pubmed-meshheading:14700633-Xenopus
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
GSK-3-selective inhibitors derived from Tyrian purple indirubins.
|
|
pubmed:affiliation |
CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff cedex, Bretagne, France. meijer@sb-roscoff.fr
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
