Novel 8-arylated purines as inhibitors of glycogen synthase kinase.

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Ibrahim N, Mouawad L, Legraverend M

Novel 8-arylated purines as inhibitors of glycogen synthase kinase.

Eur J Med Chem. 2010 Aug;45(8):3389-93. doi: 10.1016/j.ejmech.2010.04.026. Epub 2010 Apr 28.

PubMed ID

20472330 [ View in PubMed

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Abstract

A series of 8-arylated purine derivatives bearing either an aniline or an alkyl amide at position 6 were found to inhibit glycogen synthase kinase-3, with good selectivity over ten kinases. Molecular modeling studies indicated that the most active compounds (8a and 8e), adopt a planar conformation, close to the shape of AMPPNP in the crystal structure of GSK-3. These compounds are stabilized by hydrophobic contacts between the 8-aromatic group and the protein adenine pocket and by electrostatic contacts.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Staurosporine	Glycogen synthase kinase-3 beta	IC 50 (nM)	5	N/A	N/A	Details
Staurosporine	MAP kinase-activated protein kinase 2	IC 50 (nM)	36.25	N/A	N/A	Details