Indirubin-3′-oxime

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC50s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes[1][2][3].

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

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Research Areas >> Neurological Disease

Signaling Pathways >> MAPK/ERK Pathway >> JNK

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

GSK-3β

JNK1:0.8 μM (IC50)

JNK2:1.4 μM (IC50)

JNK3:1 μM (IC50)

CDK

In cerebellar granule neurons (CGNs), Indirubin-3′-oxime blocks c-Jun phosphorylation induced by potassium withdrawal and prevented CGNs from apoptosis in a dose dependent manner[1]. Indirubin-3′-oxime (IDR3O) (PC12 cells; 10 μM) significantly prevent 6OHDA-induced decrease of nuclear localized MEF2D expression[2].

Indirubin-3′-oxime (0.05 or 0.5 mg/kg; i.p.; daily for 2 or 10 weeks) enhances tibial longitudinal growth in mice without adverse changes in bone thickness parameters[3]. Animal Model: Three-week-old C57BL/6 mice[3] Dosage: 0.05 or 0.5 mg/kg Administration: I.p.; daily for 2 or 10 weeks Result: The tibial length of mice increased in a dose-dependent manner.

[1]. Xie Y, et al. Indirubin-3'-oxime inhibits c-Jun NH2-terminal kinase: anti-apoptotic effect in cerebellar granule neurons. Neurosci Lett. 2004;367(3):355-359.

[2]. Hu S, et al. Indirubin-3-Oxime Effectively Prevents 6OHDA-Induced Neurotoxicity in PC12 Cells via Activating MEF2D Through the Inhibition of GSK3β. J Mol Neurosci. 2015;57(4):561-570.

[3]. Choi S, et al. Indirubin-3'-oxime stimulates chondrocyte maturation and longitudinal bone growth via activation of the Wnt/β-catenin pathway. Exp Mol Med. 2019;51(9):1-10. Published 2019 Sep 12.