CHIR-99021 (Laduviglusib)

CatalogusnummerS1263 Batch:S126309

Afdrukken

Technische gegevens

Formule

C22H18Cl2N8
Moleculair gewicht 465.34 CAS-nr. 252917-06-9
Oplosbaarheid (25°C)* In vitro DMSO 93 mg/mL (199.85 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Voeg oplosmiddelen afzonderlijk en in volgorde toe aan het product.)
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 betekent licht oplosbaar of onoplosbaar.
* Houd er rekening mee dat Selleck de oplosbaarheid van alle verbindingen intern test en de werkelijke oplosbaarheid enigszins kan afwijken van gepubliceerde waarden. Dit is normaal en is te wijten aan lichte batch-tot-batch variaties.
* Verzending op kamertemperatuur (Stabiliteitstests tonen aan dat dit product zonder koelmaatregelen kan worden verzonden.)

Voorbereiden van stamoplossingen

Biologische activiteit

Beschrijving Laduviglusib (CHIR-99021, CT99021) is een GSK-3α en GSK-3β remmer met IC50-waarden van respectievelijk 10 nM en 6,7 nM. Het vertoont geen kruisreactiviteit tegen cycline-afhankelijke kinasen (CDK's) en toont een 350-voudige selectiviteit voor GSK-3β vergeleken met CDK's. Deze verbinding functioneert als een Wnt/β-catenin activator en induceert autophagy.
Doelen
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.

Protocol (uit referentie)

Celassay:

[1]
  • Cellijnen

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

  • Concentraties

    0.01-10 μM

  • Incubatietijd

    30 min

  • Methode

    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.
Dierstudie:

[1]
  • Dierlijke modellen

    Female db/db mice; Male ZDF rats

  • Doseringen

    8-48 mg/kg

  • Toediening

    oral administration

Referenties

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

Klantproductvalidatie

<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.

Gegevens van [ , , Med Oncol, 2017, 35(1):7 ]

Selleck's CHIR-99021 (Laduviglusib) Is geciteerd door 1086 Publicaties

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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NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.