靛玉红-3 -单肟

中文名称:

靛玉红-3 -单肟

中文同义词:

靛玉红-3;靛玉红-3 -单肟;靛玉红-3-肟;GSK-3Β抑制剂(INDIRUBIN-3-MONOXIME)

英文名称:

INDIRUBIN-3-MONOXIME

英文同义词:

3-[1,3-DIHYDRO-3-(HYDROXYIMINO)-2H-INDOL-2-YLIDENE]-1,3-DIHYDRO-2H-INDOL-2-ONE;INDIRUBIN-3-MONOXIME;INDIRUBIN-3-OXIME;Indirubine-3-oxime;INDIRUBIN-3’-MONOOXIME;Indirubin-3;Indirubin-3′;Indirubin-3

CAS号:

160807-49-8

分子式:

C16H11N3O2

分子量:

277.28

EINECS号:

相关类别:

合成;细胞生物学试剂;中药对照品;Intracellular Signaling;Aromatic Hydrazides, Hydrazines, Hydrazones and Oximes;Inhibitors;Protein Kinase

Mol文件:

160807-49-8.mol

熔点 

247-249°C

沸点 

532.2±50.0 °C(Predicted)

密度 

1.50

储存条件 

room temp

溶解度 

DMSO: >10 mg/mL

酸度系数(pKa)

8.66±0.20(Predicted)

形态

solid

稳定性

Light Sensitive

CAS 数据库

160807-49-8

生物活性

Indirubin-3-monoxime (Indirubin-3-oxime)是一种选择性的CDK抑制剂，对CDK1-cyclinB, CDK2-cyclinA, CDK2-cyclinE, CDK4-cyclinD1, CDK5-p35的IC50分别为 0.18 μM, 0.44 μM, 0.25 μM, 3.33 μM, 0.065 μM。Indirubin-3-monoxime是一种直接、选择性的5-lipoxygenase抑制剂，IC50为7.8-10 µM。

靶点

Target Value CDK5-P35 (Cell-free assay) 0.065 μM CDK1-cyclinB (Cell-free assay) 0.18 μM CDK2-cyclinE (Cell-free assay) 0.25 μM CDK2-cyclinA (Cell-free assay) 0.44 μM CDK4-cyclinD1 (Cell-free assay) 3.33 μM

Target

Value

CDK5-P35 (Cell-free assay)

0.065 μM

CDK1-cyclinB (Cell-free assay)

0.18 μM

CDK2-cyclinE (Cell-free assay)

0.25 μM

CDK2-cyclinA (Cell-free assay)

0.44 μM

CDK4-cyclinD1 (Cell-free assay)

3.33 μM

体外研究

Indirubin-3-monoxime inhibits GSK-3β by competing with ATP, with K i of 0.85 μM, and K m of 110 μM. Indirubin-3-monoxime also inhibits tau phosphorylation by GSK-3β, with an IC 50 value of around 100 nM. Indirubin-3-monoxime completely inhibits the phosphorylation of the AT100 epitope. Indirubin-3-monoxime inhibits vascular smooth muscle cell (VSMC) proliferation with IC 50 of ∼2 µM. Indirubin-3-monoxime blunts migration of VSMC stimulated with the PDGF. Indirubin-3-monoxime interferes with the migratory response in VSMC, and also suppresses the production of pro-migratory LT in monocytes. Moreover, Indirubin-3-monoxime inhibits 5-lipoxygenase (5-LO) product synthesis in monocytes and neutrophils, with the same potency (IC 50 =5.0±1.1 and 3.7±1.2 µM, respectively). Indirubin-3-monoxime is an inhibitor of 5-LO, with IC 50 of 7.8-10 µM in cell-free assay.

体内研究

Indirubin-3-monoxime (0.1, 0.2 and 0.4 mg/kg, i.p) dose dependently reverses the cognitive impairment and combats the elevated oxidative stress markers in HFD fed mice. Indirubin-3-monoxime also dose dependently lowers the serum glucose, TGs, TC and insulin levels, and improves the β-cell functioning in HFD fed mice. Moreover, Indirubin-3-monoxime treatment significantly decreases HOMA-IR levels compared to HFD group. Indirubin-3-monoxime (0.4 mg/kg) significantly attenuates the increased EL in the HFD group.

用途 

A potent inhibitor of GSK-3脽 (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 (10眉M).

WGK Germany 

3