GSK3-IN-3

GSK3-IN-3 is a mitophagy inducer, inducing Parkin-dependent mitophagy. GSK3-IN-3 is also a GSK-3 inhibitor with an IC50 value of 3.01 μM. GSK3-IN-3 is non-ATP nor substrate competitive and is neuroprotective against 6-OHDA[1][2][3].

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Signaling Pathways >> Autophagy >> Mitophagy

Research Areas >> Neurological Disease

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

IC50: 3.01 μM (GSK-3)[3]

GSK3-IN-3 (VP07)（25 μM；24 小时）在表达 Parkin 的 U2OS-iMLS 细胞中诱导线粒体自噬，但效力有限[1]。 GSK3-IN-3（1.56-25 μM；24 小时）导致 U2OS-iMLS-Parkin 细胞发生线粒体分裂和线粒体形态变化[1]。 GSK3-IN-3 (VP0.7)（5 μM，10 μM；）在 SH-SY5Y 细胞的帕金森病体外细胞模型中显示出针对 6-OHDA 的神经保护作用[2]。< br/> Immunofluorescence[1] Cell Line: Parkin-expressing U2OS-iMLS cells Concentration: 1.56 μM, 3.12 μM, 6.25 μM, 12.5 μM, and 25 μM; Incubation Time: 24 hours Result: Induced a mitochondrial morphology change from a filament-shaped network to a more round-shaped network. Cell Viability Assay[2] Cell Line: SH-SY5Y cells Concentration: 0.5 μM, 1 μM, 3 μM, 5 μM, and 10 μM Incubation Time: 16 hours; with 35 μM 6-OHDA Result: Inhibited cell growth with an IC50 value of 2.57 μM.

[1]. Maestro I, et al. Phenotypic Assay Leads to Discovery of Mitophagy Inducers with Therapeutic Potential for Parkinson's Disease. ACS Chem Neurosci. 2021 Dec 15;12(24):4512-4523.  

[2]. Morales-García JA, et al. Glycogen synthase kinase-3 inhibitors as potent therapeutic agents for the treatment of Parkinson disease. ACS Chem Neurosci. 2013 Feb 20;4(2):350-60.  

[3]. Palomo V, et al. Exploring the binding sites of glycogen synthase kinase 3. Identification and characterization of allosteric modulation cavities. J Med Chem. 2011 Dec 22;54(24):8461-70.