Indirubin-3'-oxime

Indirubin-3’-oxime is a potent inhibitor of glycogen synthase kinase 3β (GSK3β; IC₅₀ = 22 nM). As GSK3β phosphorylates tau protein, indirubin-3’-oxime prevents tau phosphorylation both in vitro and in vivo at Alzheimer’s disease-relevant sites. It also inhibits cyclin-dependent kinases (CDKs) at higher concentrations, including Cdk1/cyclin B (IC₅₀ = 180 nM), Cdk2/cyclin A (IC₅₀ ~500 nM), Cdk2/cyclin E (IC₅₀ = 250nM), Cdk4/cyclin D1 (IC₅₀ = 3.3 μM) and Cdk5/p35 (IC₅₀ = 100 nM). Indirubin-3’-oxime reversibly inhibits the proliferation of many cells types, arresting cycling in the G₂/M phase.

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Indirubin-3′-oxime has been used in the inhibition of glycogen synthase kinase 3 in human monocytic cell line, THP-1.

A potent inhibitor of GSK-3 (IC50=22nM). Also inhibits CDK1 (IC50=180nM) and CDK (IC50=100nM). It reversibly arrests asynchronous HBL-100 cells at G2. It induces apoptosis in the mammary carcinoma cell line MCF-7 (10üM).

ChEBI: Indirubin-3'-monoxime is a member of the class of biindoles that is indirubin in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime. It has a role as an EC 2.7.11.22 (cyclin-dependent kinase) inhibitor, an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, an osteogenesis regulator, a neuroprotective agent and an anti-obesity agent. It is a member of oxindoles, a bisindole, a ring assembly, a ketoxime and an alkaloid.

Protein kinase inhibitor: inhibits cyclin-dependent kinases (IC 50 = 0.18-3.33 μ M) and GSK-3 β (IC 50 = 0.19 μ M). Inhibits CDK5- and GSK-3 β -mediated tau phosphorylation, a process over-active in Alzheimer disease states. Also inhibits AMPK, LCK and SGK. Induces cell cycle arrest and inhibits cell proliferation.

Indirubin-3′-oxime is a cyclin-dependent kinase inhibitor which functions by competing with ATP for binding to the catalytic subunit; exhibits antiproliferative activity leading to G2/M arrest in many cell lines and G1/S arrest in Jurkat cells.

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[1] S LECLERC. Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors[J]. The Journal of Biological Chemistry, 2001, 276 1: 251-260. DOI:10.1074/jbc.m002466200
[2] EVE DAMIENS. Anti-mitotic properties of indirubin-3′-monoxime, a CDK/GSK-3 inhibitor: induction of endoreplication following prophase arrest[J]. Oncogene, 2001, 20 29: 3786-3797. DOI:10.1038/sj.onc.1204503
[3] JIN-KYUNG KIM. Indirubin-3’-monoxime, a derivative of a chinese antileukemia medicine, inhibits angiogenesis[J]. Journal of cellular biochemistry, 2011, 112 5: 1384-1391. DOI:10.1002/jcb.23055
[4] YUN DING  Guo H F  Aimin Qiao. Indirubin-3’-monoxime rescues spatial memory deficits and attenuates β-amyloid-associated neuropathology in a mouse model of Alzheimer’s disease[J]. Neurobiology of Disease, 2010, 39 2: Pages 156-168. DOI:10.1016/j.nbd.2010.03.022