生物活性

• 靶点	GSK-3 Ki:9nM

• 描述GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3 and subunit, which plays a key role in many different biological processes including tumorigenesis, cell survival, and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/-catenin signaling^[2][3]. SB-216763 is a maleimide-derived GSK-3 inhibitor with IC50 value of 34nM for GSK-3K (measured by recombinant human GSK-3K). SB-216763 is equally effective at inhibiting GSK-3 and SB-216763<6uM can induce transcription of a-catenin-LEF/TCF regulated reporter gene dose-dependently in serum starved HEK293 for 16h ^[1]. Treatment with 5uM SB-216763 for 4h can increase levels of cytoplasmic-catenin, which is a target negatively regulated by GSK-3, in both serum-starved cerebellar granule neurons and HEK293 cells. SB-216763 (3-5uM) can confer a marked reduction in GSK-3-dependent tau phosphorylation at Ser202-phosphoepitopes in transfected HEK293 cells and endogenous tau protein in cerebellar granule neurons^[4]. SB-216763 can cross the blood–brain barrier and enter the CNS in both rodents and nonhuman primates^[5]. Co-infusion of SB-216763 corrected all responses to Aβ infusion except the induction of gliosis and behavioral deficits in the Morris water maze of rats ^[6].
• 作用机制Mechanism: SB-216763 can inhibit GSK-3 in an ATP competitive manner. ^[1]