| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Indirubin-3'-monoxime is a novel, potent and selective inhibitor of GSK-3β (glycogen synthase kinase 3β) which also weakly inhibits 5-Lipoxygenase with IC50s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC50s of 100 and 180 nM. As GSK3β phosphorylates tau protein, indirubin-
| Targets |
GSK-3β (IC50 = 22 nM); CDK5/p25 (IC50 = 100 nM); CDK1/cyclin B (IC50 = 180 nM); 5-LOX (IC50 = 7.8-10 μM)
|
|---|---|
| ln Vitro |
Indirubin-3'-monoxime has a Ki of 0.85 μM and a Km of 110 μM. It inhibits GSK-3β by complementation with ATP. Even with an IC50 value of about 100 nM, indirubin-3'-monoxime still prevents tau phosphorylation by GSK-3{. At the AT100 epitope, phosphorylation is totally inhibited by indiviubunin-3'-monoxime [1]. An IC50 of approximately 2 μM is observed for indinabinin-3'-monoxime's inhibition of vascular smooth muscle cell (VSMC) proliferation. VSMC migration induced by PDGF was inhibited by indorubin-3'-monoxime]. Both the generation of LT in monocytes that promotes migration and the migration response in VSMC are disrupted by indorubin-3'-monoxime. Furthermore, with comparable efficacy (IC50 values of 5.0±1.1 and 3.7±1.2μM, respectively), indirubin-3'-monoxime impedes the production of 5-lipoxygenase (5-LO) products in monocytes and neutrophils. With an IC50 of 7.8-10 μM in cell-free experiments, indorubin-3'-monoxime is a 5-LO reagent [3].
|
| ln Vivo |
In breast milk fed on a high-fat diet, indirubin-3'-monoxime (0.1, 0.2, and 0.4 mg/kg, ip) preventatively cures cognitive impairment and counteracts heightened oxidative midday indicators. In addition, dose-dependent reductions in insulin, TG, TC, and plasma glucose were observed when lactations given a high-fat diet (HFD) had better β-cell function. In addition, HOMA-IR levels were considerably lower in the Indirubin-3'-monoxime group as compared to the HFD group. The elevated EL in the HFD group was considerably reduced by -3'-Monoxime (0.4 mg/kg) [2].
|
| Enzyme Assay |
GSK-3β is expressed in and purified from insect Sf9 cells. It is measured with a final volume of 30 μL of 15 μM[γ-32P]ATP (3000 Ci/mmol; 1 mCi/L) after a 1/100 dilution in 1 mg/mL BSA, 10 mM DTT, and 5 μL of 40 μM GS-1 peptide as a substrate. Following a 30-minute incubation at 30°C, 25-μL aliquots of the supernatant are spotted onto pieces of Whatman P81 phosphocellulose paper that are 2.5 x 3 cm. Twenty seconds later, the filters are washed five times (for at least five minutes each time) in a solution of 10 mL of phosphoric acid/liter of water. A 1 mL sample of ACS scintillation fluid is used to count the wet filters[1].
|
| Cell Assay |
Cytotoxicity of Indirubin-3'-monoxime in monocytes is analysed by MTT assay in a 96-well format using a multi-well scanning spectrophotometer. Following a 30-minute incubation with Indirubin-3'-monoxime, neutrophils (5 106 cells/mL) or monocytes (2 106 cells/mL) are tested for cell viability using the MTT assay. There is no detectable acute cytotoxicity when compared to vehicle (0.3% DMSO) in neutrophils (103.94.4%; 129.45.4%; n=3, each)[3].
|
| Animal Protocol |
Male mice (5–6 weeks old) are divided into five groups (n=10) at random. Groups 1 and 2 receive a normal pellet diet (NPD); Groups 3 through 5 receive a HFD; and Groups 6 through 9 receive an Indirubin-3'-monoxime treatment (0.1, 0.2, and 0.4 mg/kg i.p., respectively) once daily for one week after receiving the HFD for 8 weeks. In (2.5% v/v) DMSO in saline, indorubin-3'-monoxime is dissolved. Equal volumes of vehicle (2.5% v/v DMSO in saline) are administered to the mice in the NPD and HFD groups. Indirubin-3'-monoxime dosages are decided upon. Mice are kept for eight weeks in standard husbandry conditions (22°C and 60% humidity) with free access to food and water on a 12/12-hour light/dark cycle. Throughout the course of the experiment, weekly weight checks are made[2].
|
| References |
[1]. Leclerc S, et al. 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. 2001 Jan 5;276(1):251-60.
[2]. Sharma S, et al. Neuroprotective role of Indirubin-3'-monoxime, a GSKβ inhibitor in high fat diet induced cognitive impairment in mice. Biochem Biophys Res Commun. 2014 Oct 3;452(4):1009-15. [3]. Blazevic T, et al. Indirubin-3'-monoxime exerts a dual mode of inhibition towards leukotriene-mediated vascular smooth muscle cell migration. Cardiovasc Res. 2014 Mar 1;101(3):522-32. [4]. Cao Z, et al. Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer [published online ahead of print, 2021 Oct 8]. J Med Chem. 2021;10.1021/acs.jmedchem.1c01311 |
| Molecular Formula |
C16H11N3O2
|
|---|---|
| Molecular Weight |
277.2774
|
| Exact Mass |
277.0851
|
| Elemental Analysis |
C, 69.31; H, 4.00; N, 15.15; O, 11.54
|
| CAS # |
160807-49-8
|
| Related CAS # |
Indirubin;479-41-4
|
| Appearance |
Solid powder
|
| SMILES |
O=C1NC2=C(C=CC=C2)/C1=C3NC4=C(C=CC=C4)C/3=N/O
|
| InChi Key |
HBDSHCUSXQATPO-BRNLPKLHSA-N
|
| InChi Code |
InChI=1S/C16H11N3O2/c20-16-13(9-5-1-3-7-11(9)18-16)15-14(19-21)10-6-2-4-8-12(10)17-15/h1-8,17,21H,(H,18,20)/b15-13-,19-14-
|
| Chemical Name |
3-[1,3-dihydro-3-(hydroxyimino)-2H-indol-2-ylidene]-1,3-dihydro-2H-indol-2-one
|
| Synonyms |
Indirubin-3’-oxime
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~125 mg/mL (450.8 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6065 mL | 18.0323 mL | 36.0646 mL | |
| 5 mM | 0.7213 mL | 3.6065 mL | 7.2129 mL | |
| 10 mM | 0.3606 mL | 1.8032 mL | 3.6065 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA