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.
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
Nature. 2022 Jul;607(7917):149-155.
Deciphering the immunopeptidome in vivo reveals new tumour antigens
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
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Source | Sci Rep (2015). Figure 3. CHIR-99021 |
| Method | qPCR | |
| Cell Lines | J1 mESCs and F9 mEC cells | |
| Concentrations | 3 μM | |
| Incubation Time | 24 h | |
| Results | By contrast, all of the ESCC miRNAs were downregulated by CHIR (Fig. 3a–e). The miR-200b-429 and miR-183-182 clusters, which are highly expressed in pluripotent cells, were downregulated by both BIO and CHIR (Fig. 3f, 3g). |
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Source | Sci Rep (2015). Figure 1. CHIR-99021 |
| Method | immunofluorescence staining | |
| Cell Lines | J1 mESCs and F9 mEC cells | |
| Concentrations | 3 μM | |
| Incubation Time | 24 h | |
| Results | The relativemRNA expression level of Nanog was determined in response to BIO or CHIR in J1mESCs and F9mEC cells by qPCR. As expected, transcription of Nanog in J1 mESCs and F9 mEC cells was upregulated by both BIO and CHIR |
| Cell Experiment | |
|---|---|
| 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 | |
|---|---|
| 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.
| Related GSK-3 Products |
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| L807mts
L807mts is a substrate-competitive, potent, and highly selective GSK-3 peptide inhibitor. |
| Manzamine A
Manzamine A inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A also shows potent activity against HSV-1. |
| Manzamine A hydrochloride
Manzamine A hydrochloride inhibits specifically GSK-3β and CDK-5 with IC50s of 10.2 μM and 1.5 μM, respectively. Manzamine A hydrochloride targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A hydrochloride also shows potent activity against HSV-1. |
| CHIR 98024
CHIR 98024 (Compound L) is a glycogen synthase kinase 3 (GSK3) inhibitor with an EC50 of 0.2566 μM. |
| GSK-3 Inhibitor XIII
GSK-3 Inhibitor XIII is a potent and ATP-competitive GSK-3 inhibitor with a Ki of 24 nM. |
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