生物活性

• 靶点

  GSK-3β IC50:5nM

  GSK-3β (C199A) IC50:60nM

• 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]. Tideglusib is a thiadiazolidinedione-derived GSK-3 inhibitor with Ki value of 60nM (calculated by double ATP and inhibitor titrations) and can inhibit GSK-3 with IC50 value of 105nM (measured by enzymatic assays of human recombinant GSK-3)^[1]. Tideglusib can increase the level of phosphorylated GSK3-S9, as well as decreased the level of phosphorylated tau, in a dose or time dependent manner in GSC11 cells treated on dose of 0-10uM or in 0-6h^[4]. Tideglusib shows neuroprotection against hypoxic-ischemic brain injury in neonatal mice. Intraperitoneal administration of tideglusib (5 mg/kg) 20 min prior to the onset of ischemia can reduce cerebral infarct volume at both 24 h and 7 days after hypoxic-ischemic injury^[5]. Several clinical studies on neurological diseases, including two phase 2 studies of Alzheimer's disease, have been completed (see in https://www.clinicaltrials.gov/).
• 作用机制Tideglusib is a thiadiazolidinedione-derived non-ATP competitive inhibitor of GSK3.

• 动物研究
  剂量	Mice: min = 50 mg/kg[7], max = 200 mg/kg p.o.[8]; 5 mg/kg i.p.[5]
  给药途径	p.o., i.p.