CHIR-99021 (Laduviglusib)

Catalog No.S1263 Batch:S126311

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Technical Data

Formula

C22H18Cl2N8
Molecular Weight 465.34 CAS No. 252917-06-9
Solubility (25°C)* In vitro DMSO 93 mg/mL (199.85 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Laduviglusib (CHIR-99021, CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 values of 10 nM and 6.7 nM, respectively. It does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. This compound functions as a Wnt/β-catenin activator and induces autophagy.
Targets
GSK-3β [1]
(Cell-free assay)		 GSK-3α [1]
(Cell-free assay)
6.7 nM 10 nM
In vitro CHIR-99021 (Laduviglusib) shows greater than 500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases. Furthermore, it shows only weak binding to a panel of 22 pharmacologically relevant receptors and little inhibitory activity against a panel of 23 nonkinase enzymes. This compound induces the activation of glycogen synthase (GS) in insulin receptor-expressing CHO-IR cells with EC50 of 0.763 μM[1].
In vivo Oral administration of CHIR-99021 (Laduviglusib) at 30 mg/kg enhances glucose metabolism in a rodent model of type 2 diabetes, with a maximal plasma glucose reduction of nearly 150 mg/dl 3-4 hours after administration, while plasma insulin remains at or below control levels. When given orally at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats, this compound significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively; the higher dose also reduces hyperglycemia before the oral glucose challenge[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    Insulin receptor–expressing CHO-IR cells; Primary rat hepatocytes

  • Concentrations

    0.01-10 μM

  • Incubation Time

    30 min

  • Method

    CHIR-99021 (Laduviglusib) is used in the following procedure: CHO-IR cells expressing human insulin receptor are grown to 80% confluence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine. Trypsinized cells are seeded in 6-well plates at 1 × 10⁶ cells/well in 2 ml of medium without fetal bovine serum. After 24 h, medium is replaced with 1 ml of serum-free medium containing this compound or control (final DMSO concentration <0.1%) for 30 min at 37°C. Cells are lysed and centrifuged 15 min at 4°C/14000g. The activity ratio of GS is calculated as the GS activity in the absence of glucose-6-phosphate divided by the activity in the presence of 5 mmol/l glucose-6-phosphate, using the filter paper assay of Thomas et al.
Animal Study:

[1]
  • Animal Models

    Female db/db mice; Male ZDF rats

  • Dosages

    8-48 mg/kg

  • Administration

    oral administration

References

  • https://pubmed.ncbi.nlm.nih.gov/12606497/

Customer Product Validation

<p>For MTT assays, cells (2,000 ~ 5,000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of CHIR-99021 by adding 20 μl of 5 mg/ml 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution per 100 μl of growth medium. After incubating for 3-4 h at 37°C, the media were removed and 150 µl/well of MTT solvent (either absolute DMSO or isopropanol containing 4 mM HCl and 0.1% Nonidet-40) was added to dissolve the formazan. The absorbance of each well was measured by ELx808 (BioTek, Winooski, VT) or Wallac Victor2 (Perkin-Elmer Life Sciences, Boston, MA) Microplate Reader. Viable cells are presented as percent of control, vehicle-treated cells. </p>

, , Dr. Yong-Weon Yi from Georgetown University Medical Center

Lu1205 were treated with protein kinase inhibitors. Cell cycle protein expression was analyzed by western blot.

Data from [ , , Med Oncol, 2017, 35(1):7 ]

Selleck's CHIR-99021 (Laduviglusib) Has Been Cited by 1134 Publications

Proteogenomic characterization of non-functional pancreatic neuroendocrine tumors unravels clinically relevant subgroups [ Cancer Cell, 2025, 43(4):776-796.e14] PubMed: 40185092
Olmesartan Restores LMNA Function in Haploinsufficient Cardiomyocytes [ Circulation, 2025, 151(20):1436-1448] PubMed: 40166828
Olmesartan Restores LMNA Function in Haploinsufficient Cardiomyocytes [ Circulation, 2025, 151(20):1436-1448] PubMed: 40166828
Structure-guided discovery of highly efficient cytidine deaminases with sequence-context independence [ Nat Biomed Eng, 2025, 9(1):93-108] PubMed: 38831042
The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate [ Nat Cell Biol, 2025, 27(8):1311-1326] PubMed: 40696106
A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation [ Nat Cell Biol, 2025, NONE] PubMed: 41094030
Targeting Cardiomyocyte PCNA and POLD1 Prevents Pathologic Myocardial Hypertrophy [ Circ Res, 2025, 137(9):1160-1181] PubMed: 40948130
Microprotein PLUM encoded by Lin28b uORF is a cytoplasmic determinant of pluripotency and embryonic development [ Nat Commun, 2025, 16(1):10324] PubMed: 41298451
Identification of functional non-coding variants associated with orofacial cleft [ Nat Commun, 2025, 16(1):6545] PubMed: 40670354
AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models [ Nat Commun, 2025, 16(1):2196] PubMed: 40038304

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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