CHIR-99021 exhibits >500-fold selectivity for GSK-3 over closely related kinases. CHIR-99021 also displays >800-fold selectivity against 45 additional enzymes and receptors. CHIR-99021 (3 μM) increases free cytosolic β-catenin by 1.9-fold, mimicking the canonical Wnt signaling pathway in 3T3-L1 preadipocytes. CHIR-99021 promotes primary beta cell replication in isolated rat islets at concentrations as low as 1 μM, with 2-3 fold increase of cell replication at 5 μM of CHIR-99021 treatment. Oral administration of CHIR-99021 at 16 or 48 mg/kg 1 hour before oral glucose challenges in ZDF rats significantly improves glucose tolerance with 14% and 33% reduction in plasma glucose at 16 mg/kg and 48 mg/kg, respectively, and the higher dose of CHIR-99021 also reduces hyperglycemia before the oral glucose challenge.
Nature. 2022 Jul;607(7917):149-155.
Deciphering the immunopeptidome in vivo reveals new tumour antigens
CHIR-99021 HCl purchased from AbMole
Nat Commun. 2022 Oct 20;13(1):6230.
Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3
CHIR-99021 HCl purchased from AbMole
Mol Biol Cell. 2022 Jul 1;33(8):mbcP22031008.
Deciphering the tumor-specific immunopeptidome in vivo with genetically engineered mouse models
CHIR-99021 HCl purchased from AbMole
2020 Sep.
Developing a model to assess the contribution of cytokeratin 19-expressing cells during multipotent stromal cell-induced islet regeneration
CHIR-99021 HCl purchased from AbMole
Cell Experiment | |
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Cell lines | CHO-IR cells |
Preparation method | GS activity assays. CHO-IR cells expressing human insulin receptor, (provided by Hans Bos) were grown to 80% confluence in Hamm’s F12 medium with 10% fetal bovine serum and without hypoxanthine (34). Trypsinized cells were seeded in 6-well plates at 1 × 106 cells/well in 2 ml of medium without fetal bovine serum. After 24 h, medium was replaced with 1 ml of serum-free medium containing GSK-3 inhibitor or control (final DMSO concentration <0.1%) for 30 min at 37°C. Cells were lysed by freeze/thaw in 50 mmol/l tris (pH 7.8) containing 1 mmol/l EDTA, 1 mmol/l DTT, 100 mmol/l NaF, 1 mmol/l phenylmethylsulfonyl fluoride, and 25 μg/ml leupeptin (buffer A) and centrifuged 15 min at 4°C/14000g. The activity ratio of GS was 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. |
Concentrations | 0~500nM |
Incubation time | 30min |
Animal Experiment | |
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Animal models | fasting ZDF rats |
Formulation | 20 mmol/l citrate-buffered 15% Captisol or suspensions in 0.5% carboxymethylcellulose |
Dosages | 30 mg/kg |
Administration | oral gavage |
Molecular Weight | 501.8 |
Formula | C22H18Cl2N8.HCl |
CAS Number | 1797989-42-4 |
Solubility (25°C) | DMSO 60 mg/mL Water 6 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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FRATtide
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SAR502250
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