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| 25mg |
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Purity: ≥98%
Laduviglusib (CHIR99021; CHIR-99021) 3HCl, the trihydrochloride salt form of CHIR-99021 (also called CT99021 or CHIR-911), is a potent and orally bioavailable GSK-3α/β (glycogen synthase kinase 3α/β) inhibitor with IC50 of 10 nM/6.7 nM in cell-free assays; CHIR-99021 was proved to promote self-renewal and maintain pluripotency of both B6 and BALB/c ES cells via stabilizing the downstream effectors like c-Myc and β -catenin. In J1 mESC cells, CHIR-99021, when combined with leukemia inhibitory factor (LIF), was crucial for maintaining colony morphology and self-renewal. It has been demonstrated that CHIR-99021 controls the expression of epigenetic regulatory genes like Dnmt3 as well as several signaling pathways including Wnt/β-catenin, TGF-β, Nodal and MAPK.
| Targets |
GSK-3β (IC50 = 6.7 nM); GSK-3α (IC50 = 10 nM); ATM (cdc2 = 8800 nM)
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| ln Vitro |
Laduviglusib trihydrochloride inhibits human GSK-3β with Ki values of 9.8 nM[1]. Laduviglusib trihydrochloride is a tiny organic molecule that inhibits GSK3α and GSK3β by vying for their ATP-binding sites. Laduviglusib trihydrochloride specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases, according to in vitro kinase assays[4]. Laduviglusib trihydrochloride reduces the viability of ES-D3 cells by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM, with an IC50 of 4.9 M[2].
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| ln Vivo |
Laduviglusib (16 mg/kg or 48 mg/kg) trihydrochloride rapidly lowers plasma glucose in ZDF rats after a single oral dose, with a maximum reduction of almost 150 mg/dl occurring 3–4 h after administration[1]. Survival after 14.5 Gy abdominal irradiation (ABI) is significantly improved by laduviglusib (2 mg/kg) trihydrochloride given once 4 hours prior to radiation. Treatment with laduviglusib trihydrochloride significantly reduces crypt apoptosis, prevents the buildup of p-H2AX+ cells, and enhances crypt regeneration and villus height. Treatment with laduviglusib trihydrochloride boosts Lgr5+ cell survival by preventing apoptosis and successfully delays the loss of Olfm4, Lgr5, and CD44 as early as 4 h[5].
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| Cell Assay |
The loss of cell viability is correlated with the decline in MTT activity, a reliable metabolism-based test for estimating cell viability. In LIF-containing ES cell medium, 2,000 cells are seeded overnight on 96-well plates coated in gelatin. The medium is changed to one without LIF and with reduced serum the following day. It is also supplemented with 0.1-1 μM BIO, or 1-10 μM SB-216763, CHIR-99021, or CHIR-98014. As a control, basal medium devoid of DMSO or GSK3 inhibitors is employed. Three copies of each of the tested conditions were analyzed[3].
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| Animal Protocol |
Rats[1]:
Primary hepatocytes from male Sprague Dawley rats that weighed <140 g are prepared and used 1-3 h after isolation. Centrifuged and lysed by freeze/thaw in buffer A plus 0.01% NP40, aliquots of 1106 cells in 1 mL of DMEM/F12 medium plus 0.2% BSA and CHIR-99021 (orally at 16 or 48 mg/kg) or controls are incubated in 12-well plates for 30 min at 37°C in a CO2-enriched atmosphere. The GS assay is then carried out once more.
Mice[4]:
The mice used are 6–10 week old mice. The PUMA+/+ and PUMA-/- littermates of Lgr5-EGFP (Lgr5-EGFP-IRES-creERT2) mice are either given abdominal irradiation (ABI) or whole body irradiation (TBI) to induce radiation sickness. Two milligrams per kilogram of CHIR99021 or one milligram per kilogram of SB415286 are intraperitoneally (i.p.) injected into mice four hours prior to radiation treatment. Small intestines are removed from sacrificed mice and subjected to western blotting and histology tests. Before being sacrificed, all mice receive an intraperitoneal injection of 100 mg/kg BrdU.
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| References |
| Molecular Formula |
C22H21CL5N8
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|---|---|
| Molecular Weight |
574.72
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| Exact Mass |
574.72
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| Elemental Analysis |
C, 45.98; H, 3.68; Cl, 30.84; N, 19.50
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| CAS # |
1782235-14-6
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| Related CAS # |
Laduviglusib;252917-06-9;Laduviglusib monohydrochloride;1797989-42-4
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| Appearance |
Solid powder
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| SMILES |
CC1=CN=C(N1)C2=CN=C(N=C2C3=C(C=C(C=C3)Cl)Cl)NCCNC4=NC=C(C=C4)C#N.Cl.Cl.Cl
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| InChi Key |
DSFVSCNMMZRCIA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H18Cl2N8.3ClH/c1-13-10-29-21(31-13)17-12-30-22(32-20(17)16-4-3-15(23)8-18(16)24)27-7-6-26-19-5-2-14(9-25)11-28-19;;;/h2-5,8,10-12H,6-7H2,1H3,(H,26,28)(H,29,31)(H,27,30,32);3*1H
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| Chemical Name |
6-[2-[[4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2-yl]amino]ethylamino]pyridine-3-carbonitrile;trihydrochloride
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| Synonyms |
CHIR-73911 3HCl; CHIR911;CHIR 911; CT- 99021; CT-99021; CHIR73911; CHIR 73911 trihydrochloride; CHIR-911; CT- 99021; GSK 3 inhibitor XVI; GSK 3IXV; CHIR99021; CHIR 99021
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.62 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7400 mL | 8.6999 mL | 17.3998 mL | |
| 5 mM | 0.3480 mL | 1.7400 mL | 3.4800 mL | |
| 10 mM | 0.1740 mL | 0.8700 mL | 1.7400 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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