INDIRUBIN-3'-MONOXIME Chemical Properties

Melting point:

247-249°C

Boiling point:

532.2±50.0 °C(Predicted)

Density 

1.50

storage temp. 

room temp

solubility 

DMSO: >10 mg/mL

form 

solid

pka

8.66±0.20(Predicted)

color 

Dark red or brown

Stability:

Light Sensitive

CAS DataBase Reference

160807-49-8

Safety Information

WGK Germany 

3

MSDS

• Language:English Provider:SigmaAldrich

INDIRUBIN-3'-MONOXIME Usage And Synthesis

Description

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.

Chemical Properties

Dark Red Solid

Uses

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

Uses

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).

Definition

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.

Biological Activity

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.

Biochem/physiol Actions

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.

storage

Store at RT

References

1) Leclerc?et al. (2001),?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. Biol. Chem.,?276?251 2) Damiens?et al. (2001),?Anti-mitotic properties of indirubin-3′-monoximine, a CDK/GSK-3 inhibitor: induction of endoreplication following prophase arrest; Oncogene,?20?3786 3) Kim?et al. (2011),?Indirubin-3′-monoxime, a derivative of a chinese antileukemia medicine, inhibits angiogenesis; J. Cell. Biochem.,?112?1384 4) Ding?et al. (2010),?Indirubin-3′-monoxime rescues spatial memory deficits and attenuates beta-amyloid-associated neuropathology in a mouse model of Alzheimer’s disease; Neurobiol. Dis.,?39?156

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