Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-4190
Chem Biol 2003 Dec 01;1012:1255-66. doi: 10.1016/j.chembiol.2003.11.010.
Show Gene links Show Anatomy links

GSK-3-selective inhibitors derived from Tyrian purple indirubins.

Meijer L , Skaltsounis AL , Magiatis P , Polychronopoulos P , Knockaert M , Leost M , Ryan XP , Vonica CA , Brivanlou A , Dajani R , Crovace C , Tarricone C , Musacchio A , Roe SM , Pearl L , Greengard P .


???displayArticle.abstract???
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.

???displayArticle.pubmedLink??? 14700633
???displayArticle.link??? Chem Biol


Species referenced: Xenopus
Genes referenced: gsk3b

References :
Fischer, CDK versus GSK-3 inhibition: a purple haze no longer? 2003, Pubmed