GSK-3β inhibitor 13

Names

[ CAS No. ]:
2227316-74-5

[ Name ]:
GSK-3β inhibitor 13

Biological Activity

[Description]:

GSK-3β inhibitor 13 (compound 47) is an orally active and potent GSK-3β inhibitor with blood-brain permeability. GSK-3β inhibitor 13 inhibits GSK-3β and GSK-3α with IC50s of 0.73 nM and 0.35 nM, respectively. GSK-3β inhibitor 13 significantly decreases the phosphorylation of tau (IC50=58 nM), which leads the formation of the neurofibrillary tangles associated with Alzheimer's disease[1].

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> GSK-3
Signaling Pathways >> Epigenetics >> PKC
Signaling Pathways >> JAK/STAT Signaling >> Pim
Research Areas >> Neurological Disease
Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3
Signaling Pathways >> TGF-beta/Smad >> PKC

[Target]

GSK-3β:0.73 nM (IC50)

GSK-3α:0.35 nM (IC50)

PKCθ:0.36 μM (IC50)

PIM1:0.38 μM (IC50)

AAK1:0.20 μM (IC50)


[In Vivo]

GSK-3β inhibitor 13 在血浆中的暴露量为 3.8 μM，在脑中的暴露量为 1.3 μM，导致脑-血浆 (B/P) 比率为 0.34[1]。 GSK-3β inhibitor 13 (30 mg/kg；口服；单剂量) 在 LaFerla 3xTg-C57BL6 小鼠中降低 52% 的 pTau396 水平[1]。 在小鼠中的药代动力学分析[1] Route Dose (mg/kg) CL (mL/mL/kg) Vss (L/kg) MRT (h) t1/2 (h) i.v. 2 3.8 1.1 4.8 5.2 Route Dose (mg/kg) AUCtot (μM·h) Cmax (μM) F (%) p.o. 10 68.3 7.8 64

[References]

[1]. Hartz RA, et al. Design, Structure-Activity Relationships, and In Vivo Evaluation of Potent and Brain-Penetrant Imidazo[1,2-b]pyridazines as Glycogen Synthase Kinase-3β (GSK-3β) Inhibitors. J Med Chem. 2023 Mar 23;66(6):4231-4252.  

Chemical & Physical Properties

[ Molecular Formula ]:
C23H22N6O2

[ Molecular Weight ]:
414.46

Related Compounds