CHIR-98014 |
Catalog No.GC12176
One-Click Copy Product Info
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CHIR-98014 is a potent, cell-permeable inhibitor of GSK-3α and GSK-3β with IC50 values of 0.65nM and 0.58nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 252935-94-7
Sample solution is provided at 25 µL, 10mM.
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CHIR-98014 is a potent, cell-permeable inhibitor of GSK-3α and GSK-3β with IC50 values of 0.65nM and 0.58nM, respectively[1]. GSK-3 (glycogen synthase kinase 3) is a serine/threonine protein kinase and plays a key role in many central intracellular signaling pathways, including cell proliferation, migration, inflammation and immune response, glucose regulation, and apoptosis[2, 3]. CHIR-98014 can regulate the Wnt/β-catenin signaling pathway and has a wide range of applications in stem cell maintenance, metabolic diseases, and neurodegenerative disease research[4].
In vitro, pretreatment of cortical and hippocampal neurons with CHIR-98014 (10μM) for 1h significantly reduced PrP1-30-induced neurite loss and significantly reduced the number of dead cells[5]. Treatment of A549 cells with CHIR-98014 (0.25-2μM) for 48h inhibited phosphorylation of Ser46 and Ser392 (p53 activation markers) induced by actinomycin D and Nutlin-3a (A+N), but made the cells sensitive to A+N-induced apoptosis[6].
In vivo, oral treatment of HepG2 liver cancer cell xenograft mice with CHIR-98014 (10mg/kg) for 15 days significantly inhibited tumor growth in mice, and combined with Hjp-6-171, it exerted a synergistic effect[7]. Oral treatment of NSG mice with KMT2A rearranged leukemia with CHIR-98014 (15mg/kg) partially inhibited the tumor burden of mice and significantly prolonged the survival of mice[8].
References:
[1] Ring D B, Johnson K W, Henriksen E J, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo[J]. Diabetes, 2003, 52(3): 588-595.
[2] Pan W A, Tsai H Y, Wang S C, et al. The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression[J]. RNA biology, 2015, 12(3): 255-267.
[3] Jope R S, Yuskaitis C J, Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics[J]. Neurochemical research, 2007, 32: 577-595.
[4] Phukan S, Babu V S, Kannoji A, et al. GSK3β: role in therapeutic landscape and development of modulators[J]. British journal of pharmacology, 2010, 160(1): 1-19.
[5] Zajkowski T, Nieznanska H, Nieznanski K. Stabilization of microtubular cytoskeleton protects neurons from toxicity of N-terminal fragment of cytosolic prion protein[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2015, 1853(10): 2228-2239.
[6] Łasut-Szyszka B, Małachowska B, Gdowicz-Kłosok A, et al. Transcriptome Analysis of Cells exposed to actinomycin D and Nutlin-3a reveals new candidate p53-Target genes and indicates that CHIR-98014 is an important inhibitor of p53 activity[J]. International Journal of Molecular Sciences, 2021, 22(20): 11072.
[7] Liu Y, Xue M, Cao D, et al. Multi-omics characterization of WNT pathway reactivation to ameliorate BET inhibitor resistance in liver cancer cells[J]. Genomics, 2021, 113(3): 1057-1069.
[8] Wright S, Hu J, Wang H, et al. Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens[J]. Proceedings of the National Academy of Sciences, 2023, 120(16): e2220134120.
| Cell experiment [1]: | |
Cell lines | Cortical and hippocampal neurons |
Preparation Method | To stabilize the microtubule cytoskeleton, cells were pretreated with the GSK-3 inhibitor CHIR-98014 (10μM) for 1h and then incubated in the presence or absence of 20μM PrP1-30 for 12h. Confocal microscopy was used to observe cortical and hippocampal neurons. |
Reaction Conditions | 10μM; 1h |
Applications | Treatment of the cortical as well as hippocampal neurons with 10μM CHIR-98014 prevents loss of neurites caused by 20μM PrP1-30. |
| Animal experiment [2]: | |
Animal models | Male CB17-SCID mice |
Preparation Method | Male CB17-SCID mice were inoculated with HepG2 cells subcutaneously to establish HepG2 mice subcutaneously transplanted tumor models. Twenty-three days after inoculation, the tumor-bearing mice were divided into 3 groups according to the size of the tumor by the random block method, with 3 mice in each group: CHIR-98014 (10mg/kg) group, Hjp-6-171 (50mg/kg) group and the drug combination group (CHIR-98014 10mg/kg+Hjp-6-171 50mg/kg). Average tumor volume in each group after grouping was about 194mm3. Each group was administered by daily intragastric administration of corresponding inhibitors at a dose of 10mL/kg for 15 days. At the end of the experiment, animals were euthanized with CO2, and subcutaneous tumor tissues were quickly stripped and weighed. |
Dosage form | 10mg/kg; 15 days; p.o. |
Applications | Either treatment with Hjp-6-171 or CHIR-98014 alone could inhibit tumor growth in vivo, combination therapy had a synergistic effect. |
References: | |
| Cas No. | 252935-94-7 | SDF | |
| Chemical Name | 6-N-[2-[[4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-yl]amino]ethyl]-3-nitropyridine-2,6-diamine | ||
| Canonical SMILES | C1=CC(=C(C=C1Cl)Cl)C2=NC(=NC=C2N3C=CN=C3)NCCNC4=NC(=C(C=C4)[N+](=O)[O-])N | ||
| Formula | C20H17Cl2N9O2 | M.Wt | 486.31 |
| Solubility | ≥ 8.1mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0563 mL | 10.2815 mL | 20.563 mL |
| 5 mM | 411.3 μL | 2.0563 mL | 4.1126 mL |
| 10 mM | 205.6 μL | 1.0282 mL | 2.0563 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)