CHIR-99021 (Laduviglusib)

N. catalogoS1263 Lotto:S126309

Stampa

Dati tecnici

Formula

C22H18Cl2N8
Peso molecolare 465.34 Numero CAS 252917-06-9
Solubilità (25°C)* In vitro DMSO 93 mg/mL (199.85 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Aggiungere i solventi al prodotto singolarmente e in ordine.)
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 significa leggermente solubile o insolubile.
* Si prega di notare che Selleck testa la solubilità di tutti i composti internamente e la solubilità effettiva può differire leggermente dai valori pubblicati. Ciò è normale ed è dovuto a leggere variazioni da lotto a lotto.
* Spedizione a temperatura ambiente (I test di stabilità mostrano che questo prodotto può essere spedito senza alcuna misura di raffreddamento.)

Preparazione delle soluzioni stock

Attività biologica

Descrizione Laduviglusib (CHIR-99021, CT99021) è un inibitore di GSK-3α e GSK-3β con valori di IC50 di 10 nM e 6,7 nM, rispettivamente. Non mostra reattività crociata contro le chinasi ciclina-dipendenti (CDK) e mostra una selettività 350 volte superiore verso GSK-3β rispetto alle CDK. Questo composto funziona come attivatore di Wnt/β-catenin e induce l'autophagy.
Target
GSK-3β
(Cell-free assay)		 GSK-3α
(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.
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.

Protocollo (da riferimento)

Saggio cellulare:

[1]
  • Linee cellulari

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

  • Concentrazioni

    0.01-10 μM

  • Tempo di incubazione

    30 min

  • Metodo

    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.
Studio sugli animali:

[1]
  • Modelli animali

    Female db/db mice; Male ZDF rats

  • Dosaggi

    8-48 mg/kg

  • Somministrazione

    oral administration

Riferimenti

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

Convalida del prodotto da parte del cliente

<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.

Dati da [ , , Med Oncol, 2017, 35(1):7 ]

Selleck's CHIR-99021 (Laduviglusib) È stato citato da 1086 Pubblicazioni

GLIS2 Promotes Epithelial-Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β-Catenin Pathway [ The Kaohsiung Journal of Medical Sciences, September 12, 2025, e70103]
Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis [ Journal of the American Heart Association, October 2, 2017, e005295] PubMed: 28971953
The Glycogen Synthase Kinase-3 Inhibitor CHIR99021 Reduces Fatty Infiltration and Muscle Atrophy After Rotator Cuff Tears: An In Vitro Experiment and In Vivo Mouse Model [ The American Journal of Sports Medicine, February 24, 2025, 1184-1194]
Pre-adaptation of stem cell-derived islet organoids to hypoxia via zinc transportation inhibition drives angiogenesis [ Cell Stem Cell, 2026, 33(4):676-694.e10] PubMed: 41932324
Histone H3.3 phosphorylation facilitates H3K9me3-heterochromatin formation during retrotransposon silencing and X-chromosome inactivation via H3.3K27me3-CBX7-KAP1 axis [ Sci Bull (Beijing), 2026, 71(4):820-837] PubMed: 41582043
Neural crest cell-derived DKK1 and NEDD4 modulate Wnt signalling in the second heart field to orchestrate outflow tract development [ Nat Commun, 2026, 17(1):1751] PubMed: 41571667
Epitranscriptomic regulation of mRNA stability in pivotal transcription factors modulates the second cell fate decision [ Nat Commun, 2026, 17(1):5800] PubMed: 42045194
Modeling early human heart development using an iPSC-based 3D bioprinted model of embryonic heart tube [ Nat Commun, 2026, 17(1):5689] PubMed: 42031752
Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders [ Mol Cell, 2026, 86(4):604-624.e16] PubMed: 41653922
Endogenous retroviral elements LTR8B and MER65 rewire PSG9 regulation to control trophoblast syncytialization and pre-eclampsia risk [ Genome Biol, 2026, 27(1)73] PubMed: 41796334

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