AR-A014418 (SN-4521; GSK 3β inhibitor VIII)

Alias: GSK-3β Inhibitor VIII; GSK-3beta Inhibitor VIII; SN 4521; SN-4521; SN4521; AR-A014418; AR-A 014418; AR-A-014418; AR-AO-14418;
Cat No.:V0221 Purity: ≥98%
AR-A014418 (AR 0133418; SN4521; GSK-3β inhibitor VIII; AR 014418) is a novel, potent, ATP-competitive, and selective inhibitor of GSK3β (Glycogen Synthase Kinase 3β) with the potential for neurodegenerative diseases.
AR-A014418 (SN-4521; GSK 3β inhibitor VIII) Chemical Structure CAS No.: 487021-52-3
Product category: GSK-3
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
25mg
50mg
100mg
250mg
500mg
Other Sizes

Other Forms of AR-A014418 (SN-4521; GSK 3β inhibitor VIII):

  • AR-A014418-d3
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

AR-A014418 (AR 0133418; SN4521; GSK-3 inhibitor VIII; AR 014418) is a brand-new, potent, ATP-competitive, and selective GSK3 (Glycogen Synthase Kinase 3) inhibitor with potential for treating neurodegenerative diseases. In cell-free assays, it inhibits GSK3β with an IC50 and Ki of 104 nM and 38 nM, respectively, and has minimal effects on the 26 other kinases that were also tested. By preventing Notch1 expression through inhibition of GSK-3-mediated Notch1 expression, AR-A014418 also demonstrated strong antiproliferative activity in vitro in the treatment of pancreatic cancer cells.

Biological Activity I Assay Protocols (From Reference)
Targets
GSK-3β (Ki = 38 nM); GSK-3β (Ki = 38 nM)
ln Vitro
AR-A014418 inhibits tau phosphorylation at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein with IC50 of 2.7 μM, and protects cultured N2A cells from death induced by blocking PI3K/PKB pathway. AR-A014418 prevents neurodegeneration caused by beta-amyloid peptide in hippocampal slices.[1] While in NGP and SH-5Y-SY cells, AR-A014418 lowers neuroendocrine markers and inhibits the growth of neuroblastoma cells.[2]
ln Vivo
AR-A014418 (0–4 mg/kg, i.p.) delays the onset of symptoms, enhances motor function, slows the progression of the disease, and delays the endpoint of the disease in ALS mice with the G93A mutant human SOD1. [3] Additionally, AR-A014418 inhibits mice's acetic acid and formalin-induced nociception by altering the signaling of the NMDA and metabotropic receptors as well as the transmission of TNF- and IL-1 in the spinal cord.[4]
Enzyme Assay
Calcine/propidium iodide uptake is used to determine cell viability. Calcein AM is only taken up by dead cells and becomes orange-red fluorescent when it is cleaved by esterases found within living cells. In a nutshell, N2A cells are cultured in vitro for two days before being exposed to 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 hours. Then, 2 μM PI and 1 μM calcein-AM are incubated with N2A cells for 30 min. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl2, and the cells are observed using fluorescence microscopy with a Zeiss Axiovert 135 microscope. In at least three different experiments, three fields (chosen at random) are analyzed per well (~300 cells/field). The percentage of PI-positive cells compared to all other cells is used to measure cell death. After deducting the quantity of dead cells present in vehicle-treated cultures, specific cell death is calculated in every experiment.
Cell Assay
Cell viability is assessed by calcein/propidium iodide uptake. Calcein AM is taken up and cleaved by esterases present within living cells, yielding yellowish-green fluorescence, whereas PI is only taken up by dead cells, which become orange-red fluorescent. In brief, N2A cells are cultured for 2 days in vitro and then treated with 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 h. Subsequently, N2A cells are incubated for 30 min with 2 μM PI and 1 μM calcein-AM. The cultures are then rinsed three times with Hanks buffered saline solution containing 2 mM CaCl2, and the cells are visualized by fluorescence microscopy using a Zeiss Axiovert 135 microscope. Three fields (selected at random) are analyzed per well (∼300 cells/field) in at least three different experiments. Cell death is expressed as percentage of PI-positive cells from the total number of cells. In every experiment, specific cell death is obtained after subtracting the number of dead cells present in vehicle-treated cultures.
Animal Protocol
First, 56 Tg mice are split up into four groups to study the effects of GSK-3 inhibition on the clinical symptoms, lifespan, and motor behavior function of ALS. 14 animals per group are given intraperitoneal injections of 0.5 mL of normal saline five times a week starting 60 days after birth, along with 0 μg (control group), 1 μg (group A), 2 μg (group B), or 4 μg (group C) of AR-A014418 per gram of mouse. At the endpoint outlined below, mice are sacrificed.
References

[1]. J Biol Chem. 2003 Nov 14;278(46):45937-45.

[2]. Cancer Biol Ther. 2014 May;15(5):510-5.

[3]. Exp Neurol. 2007 Jun;205(2):336-46.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C12H12N4O4S
Molecular Weight
308.3131
Exact Mass
308.05793
Elemental Analysis
C, 46.75; H, 3.92; N, 18.17; O, 20.76; S, 10.40
CAS #
487021-52-3
Appearance
Solid powder
SMILES
COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-]
InChi Key
YAEMHJKFIIIULI-UHFFFAOYSA-N
InChi Code
InChI=1S/C12H12N4O4S/c1-20-9-4-2-8(3-5-9)6-13-11(17)15-12-14-7-10(21-12)16(18)19/h2-5,7H,6H2,1H3,(H2,13,14,15,17)
Chemical Name
1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)ure
Synonyms
GSK-3β Inhibitor VIII; GSK-3beta Inhibitor VIII; SN 4521; SN-4521; SN4521; AR-A014418; AR-A 014418; AR-A-014418; AR-AO-14418;
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 Data
Solubility (In Vitro)
DMSO: ~62 mg/mL (~201.1 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 3.2435 mL 16.2174 mL 32.4349 mL
5 mM 0.6487 mL 3.2435 mL 6.4870 mL
10 mM 0.3243 mL 1.6217 mL 3.2435 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

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.

Biological Data
  • AR-A014418

    Growth inhibition by GSK-3 inhibitor AR-A014418 in neuroblastoma cells. Cancer Biol Ther. 2014 May;15(5):510-5.

  • AR-A014418

    AR-A014418 attenuation of apoptosis inhibitor expression in NGP and SH-5Y-SY cells.

  • AR-A014418

    Continuous treatment of AR-A014418 is required for growth suppression of NGP and SH-5Y-SY cells.

Contact Us