Art. -Nr.: HY-10512

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AR-A014418

(Synonyms: AR 0133418; GSK 3β inhibitor VIII; AR 014418)

21 Cited Publications

Kundenbewertung

Based on 21 publication(s) in Google Scholar

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC₅₀=104 nM; K_i=38 nM).

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Reinheit: 99.21%
CAS. Nr.: 487021-52-3
Formel: C₁₂H₁₂N₄O₄S
Molecular Weight:308.31

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

AR-A014418 Chemical Structure

CAS. Nr.: 487021-52-3

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (21)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Protokoll
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC₅₀=104 nM; K_i=38 nM)^[1].

IC₅₀ & Target^[1]

GSK-3β

104 nM (IC₅₀)

Alle GSK-3 Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
BXPC-3	IC₅₀	14 μM Compound: 77, AR-A014418	Growth inhibition of human BxPC3 cells after 72 hrs by MTS assay Growth inhibition of human BxPC3 cells after 72 hrs by MTS assay	[PMID: 19338355]
HuP-T3	IC₅₀	22 μM Compound: 77, AR-A014418	Growth inhibition of human HUPT3 cells after 72 hrs by MTS assay Growth inhibition of human HUPT3 cells after 72 hrs by MTS assay	[PMID: 19338355]
MIA PaCa-2	IC₅₀	29 μM Compound: 77, AR-A014418	Growth inhibition of human MIAPaCa2 cells after 72 hrs by MTS assay Growth inhibition of human MIAPaCa2 cells after 72 hrs by MTS assay	[PMID: 19338355]
Sf21	IC₅₀	0.104 μM Compound: AR-A014418	Inhibition of recombinant full length human GSK3beta expressed in Sf21 insect cells using biotinylated-AAEELDSRAGS(PO3H2)PQL peptide as substrate preincubated enzyme-substrate mixture for 15 to 20 mins followed by [gamma-33P]ATP addition and measured afte Inhibition of recombinant full length human GSK3beta expressed in Sf21 insect cells using biotinylated-AAEELDSRAGS(PO3H2)PQL peptide as substrate preincubated enzyme-substrate mixture for 15 to 20 mins followed by [gamma-33P]ATP addition and measured afte	[PMID: 32435391]

In Vitro

AR-A014418 blocks the phosphorylation of tau at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein, with an IC₅₀ of 2.7 μM, and protects cultured N2A cells from death cuased by PI3K/PKB pathway blockage. AR-A014418 also shows inhibitory effect on neurodegeneration mediated by beta-amyloid peptide in hippocampal slices^[1].
AR-A014418 decreases neuroendocrine markers and suppresses neuroblastoma cell growth in NGP and SH-5Y-SY cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

AR-A014418 (0-4 mg/kg, i.p.) delays the onset of symptoms, enhances motor activity, blocks disease progression, and postpons the endpoint of the disease in ALS mouse model with the G93A mutant human SOD1^[3].
AR-A014418 suppresses acetic acid- and formalin-induced nociception in mice via modulating NMDA and metabotropic receptor signaling as well as TNF-α and IL-1β transmission in the spinal cord^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Chemical Information

CAS. Nr. 487021-52-3
Appearance Solid
Molecular Weight 308.31
Formel C₁₂H₁₂N₄O₄S
Color Light yellow to yellow
SMILES

O=C(NCC1=CC=C(OC)C=C1)NC2=NC=C([N+]([O-])=O)S2
Synonyms

AR 0133418; GSK 3β inhibitor VIII; AR 014418
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (21)

All WBRT-PCRFlow CytometryCell Proliferation/Viability Assay

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Journal Impact Factor

J Exp Clin Cancer Res

Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signalling. [Abstract]

2018 Jun 25;37(1):122. PMID: 29940988

AR-A014418 purchased from MedChemExpress. Usage Cited in: J Exp Clin Cancer Res. 2018 Jun 25;37(1):122. [Abstract]

Treatment of MHCC97H cells with AR-A014418 for 24 h inhibits the expression of CD133, detected by RT-PCR.
NPJ Biofilms Microbiomes

Endogenous Coriobacteriaceae enriched by a high-fat diet promotes colorectal tumorigenesis through the CPT1A-ERK axis. [Abstract]

2024 Jan 20;10(1):5. PMID: 38245554

AR-A014418 purchased from MedChemExpress. Usage Cited in: NPJ Biofilms Microbiomes. 2024 Jan 20;10(1):5. [Abstract]

Percentage cell proliferation of CT26 cells treated with MEK inhibitor U0126-EtOH (HY-12031; 25 µM), JNK inhibitor SP600125 (HY-12041; 25 µM), P38/MAPK inhibitor SB202190 (HY-10295; 20 µM), GSK3β inhibitor TWS119 (HY-10590; 20 µM), or AR-A014418 (HY-10512; 20 µM), and vehicle or Cori.ST1911. Cell OD was measured using the CCK8 method and normalised to cell proliferation of the control. Inhibitor treatment started 4 h before Cori.ST1911 treatment. Data are represented as mean ± SEM (n = 3 independent tests), analysed by one-way analysis of variance (ANOVA) with Bonferroni’s post-hoc test. n.s., no significance.
Phytomedicine

The kava chalcone flavokawain B exerts inhibitory activity and synergizes with BCL-2 inhibition in malignant B-cell lymphoma. [Abstract]

2023 Nov:120:155074. PMID: 37716033

AR-A014418 purchased from MedChemExpress. Usage Cited in: Phytomedicine. 2023 Nov:120:155074. [Abstract]

SUDHL-4 cells were pretreated with the pan-PI3K inhibitor LY294002 (20 µM), the Akt inhibitor MK2206 (HY-108232; 4 µM), or the GSK3β inhibitor AR-A014418 (HY-10512; 10 µM) for 1 h followed by treating with FKB (Flavokawain B; HY-N2132) at 2.5 µg/ml for 24 h. Cell viability was measured using the MTS assay and results were shown as the percentage relative to the vehicle-treated control. *p < 0.05, #p < 0.01, and †p < 0.001.

AR-A014418 purchased from MedChemExpress. Usage Cited in: Phytomedicine. 2023 Nov:120:155074. [Abstract]

Raji and Jeko-1 cells were pretreated with the pan-PI3K inhibitor LY294002 (20 µM), the Akt inhibitor MK2206 (HY-108232; 4 µM), or the GSK3β inhibitor AR-A014418 (HY-10512; 10 µM) for 1 h followed by treating with FKB (Flavokawain B; HY-N2132) at 2.5 µg/ml for 24 h. Cell viability was measured using the MTS assay and results were shown as the percentage relative to the vehicle-treated control. *p < 0.05, #p < 0.01, and †p < 0.001.
Cell Syst

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations. [Abstract]

2018 Apr 25;6(4):424-443.e7. PMID: 29655704
J Transl Med

NL101 synergizes with the BCL-2 inhibitor venetoclax through PI3K-dependent suppression of c-Myc in acute myeloid leukaemia. [Abstract]

2024 Sep 27;22(1):867. PMID: 39334157
Oncogene

GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma. [Abstract]

2023 Jul;42(30):2297-2314. PMID: 37349645
Food Biosci

2026 Apr 17;80:108946.
Neurosci Bull

Engineered Alzheimer Organoids Validate the Link Between Intracellular and Soluble p-Tau Biomarkers and Highlight the Contribution of Astrocytic Tau. [Abstract]

2026 Apr 11. PMID: 41964788
Eur J Pharmacol

Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia. [Abstract]

2024 Apr 5:968:176418. PMID: 38350590
Eur J Pharmacol

Platycodin D induces apoptotic cell death through PI3K/AKT and MAPK/ERK pathways and synergizes with venetoclax in acute myeloid leukemia. [Abstract]

2023 Oct 5:956:175957. PMID: 37541375
Neuropharmacology

Hypericin alleviates high glucose-induced ferroptosis in cultured rat satellite glial cells via targeting P2X7R to activate the Akt/GSK3β/Nrf2 axis. [Abstract]

2026 Nov 1:298:111050. PMID: 42214457
FASEB J

Mechanical force modulates macrophage proliferation via Piezo1-AKT-Cyclin D1 axis. [Abstract]

2022 Aug;36(8):e22423. PMID: 35775626

AR-A014418 purchased from MedChemExpress. Usage Cited in: FASEB J. 2022 Aug;36(8):e22423. [Abstract]

AKT and GSK3β signaling was suppressed by ARQ 092 (1 μM), and phosphorylated GSK3β was activated by AR 014418 in BMDMs afterforce application.
FASEB J

Par6 regulates cell cycle progression through enhancement of Akt/PI3K/GSK-3β signaling pathway activation in glioma. [Abstract]

2020 Jan;34(1):1481-1496. PMID: 31914615
Toxicol Sci

Microcystin-Leucine-Arginine Induces Tau Pathology Through Bα Degradation via Protein Phosphatase 2A Demethylation and Associated Glycogen Synthase Kinase-3β Phosphorylation. [Abstract]

2018 Apr 1;162(2):475-487. PMID: 29228318

AR-A014418 purchased from MedChemExpress. Usage Cited in: Toxicol Sci. 2018 Apr 1;162(2):475-487. [Abstract]

Inhibition of GSK-3β enhances demethylation of PP2Ac induced by MC-LR. SH-SY5Y cells are treated with 20 μM AR-A014418 for 4 h and then treated with 10 μM MC-LR for 24 h. Levels of DM-PP2Ac and PP2Ac are measured by Western blots.
J Cell Physiol

GRK5 influences the phosphorylation of tau via GSK3β and contributes to Alzheimer's disease. [Abstract]

2019 Jul;234(7):10411-10420. PMID: 30511419
J Virol

p38MAPK- and GSK3-Mediated Phosphorylation of Snakehead Vesiculovirus Phosphoprotein at Threonine 160 Facilitates Viral Replication. [Abstract]

2023 May 31;97(5):e0040423. PMID: 37162361
J Cell Sci

LMBR1L regulates the proliferation and migration of endothelial cells through Norrin/β-catenin signaling. [Abstract]

2022 Mar 15;135(6):jcs259468. PMID: 35146515
Toxicol Appl Pharmacol

Arsenic trioxide-induced p38 MAPK and Akt mediated MCL1 downregulation causes apoptosis of BCR-ABL1-positive leukemia cells. [Abstract]

2020 Apr 17;397:115013. PMID: 32305283
Cancer Med

Proton pump inhibitors stabilize the expression of PD-L1 on cell membrane depending on the phosphorylation of GSK3β. [Abstract]

2024 May;13(10):e7083. PMID: 38752436

AR-A014418 purchased from MedChemExpress. Usage Cited in: Cancer Med. 2024 May;13(10):e7083. [Abstract]

FACS analysis was used to perform the MFI of cell membrane of PD‐L1 in H441 cells with control or multiply small molecular inhibitors (Seen in the Table 1, 24 h) (n = 3). AV412 (HY‐10346; 20, 50 nM), ERK1/2 inhibitor 1 (HY‐112287; 20, 50 nM), AR‐A014418 (HY‐10512; 100, 200 nM), Erlotinib (HY‐50896; 50, 100 nM).
SSRN

2025 Jul 25.
Research Square Preprint

2024 Jan 31.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : ≥ 100 mg/mL (324.35 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

* "≥" means soluble, but saturation unknown.

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (8.11 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

Kinase Assay^[1]

The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor in clear-bottomed microtiter plates. The biotinylated peptide substrate, biotin-AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 12 mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β-mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serum albumin/25 μL and preincubated for 10-15 min. The reaction is initiated by the addition of 0.04 μCi of [γ-³³P]ATP and unlabeled ATP in 50 mM Mg(Ac)₂ to a final concentration of 1 μM ATP and assay volume of 25 μL. Blank controls without peptide substrate are used. After incubation for 20 min at room temperature, each reaction is terminated by the addition of 25 μL of stop solution containing 5 mM EDTA, 50 μM ATP, 0.1% Triton X-100, and 0.25 mg of streptavidin-coated SPA beads corresponding to appr 35 pmol of binding capacity. After 6 h the radioactivity is determined in a liquid scintillation counter. Inhibition curves are analyzed by non-linear regression using GraphPad Prism.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay^[1]

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 (appr 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.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[3]

First, to examine the effects of GSK-3 inhibition on the clinical symptoms, life span, and motor behavior function of ALS, 56 Tg mice are divided into four groups. In each group, 0.5 mL of normal saline is mixed with either 0 μg (control group), 1 μg (group A), 2 μg (group B) or 4 μg (group C) of AR-A014418 per gram of mouse, and injected intraperitoneally into 14 animals per group 5 days a week beginning 60 days after birth. The mice are sacrificed at the endpoint described below.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (476 KB)
- English - EN (476 KB)
- Français - FR (476 KB)
- Deutsch - DE (476 KB)
- Norwegian - NO (476 KB)
- Español - ES (476 KB)
- Swedish - SV (476 KB)
- Italian - IT (476 KB)
- Korean - KR (476 KB)
- Portuguese - PT (476 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Bhat R, Xue Y, Berg S, Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003 Nov 14;278(46):45937-45. [Content Brief]

[2]. Carter YM, et al. Specific glycogen synthase kinase-3 inhibition reduces neuroendocrine markers and suppresses neuroblastoma cell growth. Cancer Biol Ther. 2014 May;15(5):510-5. [Content Brief]

[3]. Koh SH, et al. Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS. Exp Neurol. 2007 Jun;205(2):336-46 [Content Brief]

[4]. Martins DF, et al. The antinociceptive effects of AR-A014418, a selective inhibitor of glycogen synthase kinase-3 beta, in mice. J Pain. 2011 Mar;12(3):315-22. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	3.2435 mL	16.2174 mL	32.4349 mL	81.0872 mL
	5 mM	0.6487 mL	3.2435 mL	6.4870 mL	16.2174 mL
	10 mM	0.3243 mL	1.6217 mL	3.2435 mL	8.1087 mL
	15 mM	0.2162 mL	1.0812 mL	2.1623 mL	5.4058 mL
	20 mM	0.1622 mL	0.8109 mL	1.6217 mL	4.0544 mL
	25 mM	0.1297 mL	0.6487 mL	1.2974 mL	3.2435 mL
	30 mM	0.1081 mL	0.5406 mL	1.0812 mL	2.7029 mL
	40 mM	0.0811 mL	0.4054 mL	0.8109 mL	2.0272 mL
	50 mM	0.0649 mL	0.3243 mL	0.6487 mL	1.6217 mL
	60 mM	0.0541 mL	0.2703 mL	0.5406 mL	1.3515 mL
	80 mM	0.0405 mL	0.2027 mL	0.4054 mL	1.0136 mL
	100 mM	0.0324 mL	0.1622 mL	0.3243 mL	0.8109 mL

Keywords

AR-A014418

21 Cited Publications

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AR-A014418

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Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) AR-A014418

Alle GSK-3 Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (21)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

AR-A014418 Related Classifications

HY-10512 Related Classifications