CHIR 99021 trihydrochloride (Synonyms: CHIR-99021 trihydrochloride; CT99021 trihydrochloride) |
| رقم الكتالوجGC15642 |
ثلاثي هيدروكلوريد Laduviglusib (CHIR-99021) هو GSK-3α قوي وانتقائي ؛ / β ؛ مثبط مع IC50s من 10 نانومتر و 6.7 نانومتر. يظهر CHIR 99021 ثلاثي هيدروكلوريد> 500 ضعف انتقائية لـ GSK-3 على CDC2 و ERK2 وغيرها من كينازات البروتين. CHIR 99021 ثلاثي هيدروكلوريد هو أيضًا منشط Wnt / β قوي ؛ -الكاتينين لمسار الإشارات. CHIR 99021 ثلاثي هيدروكلوريد يعزز التجديد الذاتي للخلايا الجذعية الجنينية والفأر البشري. CHIR 99021 ثلاثي هيدروكلوريد يحث على البلعمة الذاتية.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1782235-14-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
CHIR-99021 trihydrochloride (CT99021 trihydrochloride) is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; >500-fold selectivity for GSK-3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases.
CHIR-99021 inhibits human GSK-3β with Ki values of 9.8 nM[1]. CHIR-99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that CHIR-99021 specifically inhibits GSK3β (IC50=~5 nM) and GSK3α (IC50=~10 nM), with little effect on other kinases[2]. In the presence of CHIR-99021 the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM CHIR-99021 with an IC50 of 4.9 μM[3].
In ZDF rats, a single oral dose of CHIR-99021 (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration[1]. CHIR99021 (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). CHIR99021 treatment significantly blocks crypt apoptosis and accumulation of p-H2AX+ cells, and improves crypt regeneration and villus height. CHIR99021 treatment increases Lgr5+ cell survival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h[4].
References:
[1]. Ring DB, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
[2]. Bennett CN, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002 Aug 23;277(34):30998-1004.
[3]. Naujok O, et al. Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.BMC Res Notes. 2014 Apr 29;7:273.
[4]. Wang X, et al. Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation. Sci Rep. 2015 Apr 10;5:8566.
|
Cell experiment: |
The viability of the mouse ES cells is determined after exposure to different concentrations of GSK3 inhibitors for three days using the MTT assay. The decrease of MTT activity is a reliable metabolism-based test for quantifying cell viability; this decrease correlates with the loss of cell viability. 2,000 cells are seeded overnight on gelatine-coated 96-well plates in LIF-containing ES cell medium. On the next day the medium is changed to medium devoid of LIF and with reduced serum and supplemented with 0.1-1 μM BIO, or 1-10 μM SB-216763, CHIR-99021 or CHIR-98014. Basal medium without GSK3 inhibitors or DMSO is used as control. All tested conditions are analyzed in triplicates[3]. |
|
Animal experiment: |
Rats[1] Primary hepatocytes from male Sprague Dawley rats that weighed PUMA+/+ and PUMA-/- littermates on C57BL/6 background (F10) and Lgr5-EGFP (Lgr5-EGFP-IRES-creERT2) mice are subjected to whole body irradiation (TBI), or abdominal irradiation (ABI). Mice are injected intraperitoneally (i.p.) with 2 mg/kg of CHIR99021 4 h before radiation or 1 mg/kg of SB415286 28 h and 4 h before radiation. Mice are sacrificed to collect small intestines for histology analysis and western blotting. All mice are injected i.p. with 100 mg/kg of BrdU before sacrifice. |
|
References: [1]. Ring DB, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95. |
|
| Cas No. | 1782235-14-6 | SDF | |
| المرادفات | CHIR-99021 trihydrochloride; CT99021 trihydrochloride | ||
| Chemical Name | (Z)-6-((2-((E)-(4-(2,4-dichlorophenyl)-5-(5-methyl-1H-imidazol-2-yl)pyrimidin-2(1H)-ylidene)amino)ethyl)imino)-1,6-dihydropyridine-3-carbonitrile trihydrochloride | ||
| Canonical SMILES | CC(N1)=CN=C1C(C(C2=C(Cl)C=C(Cl)C=C2)=N/3)=CNC3=N/CC/N=C4C=CC(C#N)=CN/4.Cl.Cl.Cl | ||
| Formula | C22H18Cl2N8.3HCl | M.Wt | 574.72 |
| الذوبان | 32 mg/mL in DMSO; 19 mg/mL in Water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.74 mL | 8.6999 mL | 17.3998 mL |
| 5 mM | 0.348 mL | 1.74 mL | 3.48 mL |
| 10 mM | 0.174 mL | 0.87 mL | 1.74 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 21 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *