AZD2858GSK-3 inhibitor,potent and selective CAS# 486424-20-8 |
- MK-4827
Catalog No.:BCC1761
CAS No.:1038915-60-4
- BMN-673 8R,9S
Catalog No.:BCC1422
CAS No.:1207456-00-5
- XAV-939
Catalog No.:BCC1120
CAS No.:284028-89-3
- PJ34
Catalog No.:BCC1865
CAS No.:344458-19-1
- ABT-888 (Veliparib)
Catalog No.:BCC1267
CAS No.:912444-00-9
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 486424-20-8 | SDF | Download SDF |
| PubChem ID | 10138980 | Appearance | Powder |
| Formula | C21H23N7O3S | M.Wt | 453.52 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 12.5 mg/mL (27.56 mM; Need ultrasonic) | ||
| Chemical Name | 3-amino-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-N-pyridin-3-ylpyrazine-2-carboxamide | ||
| SMILES | CN1CCN(CC1)S(=O)(=O)C2=CC=C(C=C2)C3=CN=C(C(=N3)C(=O)NC4=CN=CC=C4)N | ||
| Standard InChIKey | FHCSBLWRGCOVPT-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H23N7O3S/c1-27-9-11-28(12-10-27)32(30,31)17-6-4-15(5-7-17)18-14-24-20(22)19(26-18)21(29)25-16-3-2-8-23-13-16/h2-8,13-14H,9-12H2,1H3,(H2,22,24)(H,25,29) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | AZD2858 is a potent, orally active GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively, used in the research of fracture healing.In Vitro:AZD2858 (1 μM) increases β-catenin levels after a short period of time in human osteoblast cells. AZD2858 inhibits GSK-3β dependent phosphorylation with an IC50 of 68 nM. AZD2858 (10 nM) has no effect on β-catenin levels[1]. AZD2858 increases TAZ expression and osterix expression both by 1.4-fold, with EC50 of 440 nM and 1.2 μM, respectively, in hADSC. AZD2858 also induces a marked increase in osteogenic mineralisation in hADSC[3]. AZD2858 (AR28) demonstrates from 70- to greater than 6000-fold selectivity over a panel of other kinases and an IC50 of 5 nM. AR28 inhibits GSK-3 in murine cells and indicates activation of the canonical Wnt/β-catenin signaling cascade. AR28 (50, 10, and 1 nM) enhances the clonogenic ability of mesenchymal progenitors with osteogenic and adipogenic potential. AR28 (50 µM) also enhances the differentiation ability of mesenchymal progenitors to the osteogenic but not adipogenic lineage in vitro[4].In Vivo:AZD2858 (20 mg/kg) causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect[1]. AZD2858 exhibits a substantial effect on fracture healing. AZD2858 (20 mg/kg) causes an increase in cortical BMC of 9%, cortical area of 10%, and cortical thickness of 11% at 3 weeks in the non-operated right femur of rats[2]. AZD2858 (30 μmol/kg/day) alters the biomarkers of bone turnover with statistically significant increases in P1NP and decreases in TRAcP-5b seen from 3 days of treatment and onwards. AZD2858 demonstrates significant changes in serum bone turnover markers (P1NP and TRAcP-5b) and femur bone formation after only 7 days of daily dosing[3]. AZD2858 (AR28, 30 mg/kg, s.c.) stimulates an increase in an initial wave of mesenchymal progenitors with osteogenic and adipogenic potential and drives their differentiation to the osteogenic lineage in BALB/c mice. AR28 (30 mg/kg, s.c.) enhances the proliferation of committed hematopoietic progenitors and their differentiation to the osteoclast lineage but does not prevent an overall increase in bone mass[4]. References: | |||||
AZD2858 Dilution Calculator
AZD2858 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.205 mL | 11.0249 mL | 22.0497 mL | 44.0995 mL | 55.1244 mL |
| 5 mM | 0.441 mL | 2.205 mL | 4.4099 mL | 8.8199 mL | 11.0249 mL |
| 10 mM | 0.2205 mL | 1.1025 mL | 2.205 mL | 4.4099 mL | 5.5124 mL |
| 50 mM | 0.0441 mL | 0.2205 mL | 0.441 mL | 0.882 mL | 1.1025 mL |
| 100 mM | 0.022 mL | 0.1102 mL | 0.2205 mL | 0.441 mL | 0.5512 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
AZD2858 is a selective GSK-3 inhibitor with IC50 value of 68 nM.
Glycogen synthase kinase 3β (GSK-3β) plays an important role in the canonical Wnt pathway and participates in many biological processes [1].
In human osteoblast cells, AZD2858 increased β-catenin levels in a short time [1]. Incubation of hADSC with AZD2858 led to a significantly increase in osteogenic mineralisation. This indicated that inhibition of GSK-3 enhanced osteogenic differentiation of hADSC [2].
Treatment rats with AZD2858 orally increased trabecular bone mass in a dose-dependent way after a two-week treatment. The significant effect was also seen at cortical sites. Both vertebral compression strength and diaphyseal strength of femora increased in biomechanical testing. Furthermore, there was a dramatic increase in bone formation indices, serum markers of both bone formation and resorption were also elevated [1]. Also, AZD2858 drives mesenchymal cells into osteoblastic cells and leads to direct bone repair in an unstable fracture milieu [3].
References:
[1]. Marsell R, Sisask G, Nilsson Y, et al. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone, 2012, 50(3): 619-627.
[2]. Gilmour PS, O'Shea PJ, Fagura M, et al. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats. Toxicol Appl Pharmacol, 2013, 272(2): 399-407.
[3]. Sisask G, Marsell R, Sundgren-Andersson A, et al. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone, 2013, 54(1): 126-132.
- Thermopsine
Catalog No.:BCN2603
CAS No.:486-90-8
- Anagyrine
Catalog No.:BCN3049
CAS No.:486-89-5
- alpha-Isolupanine
Catalog No.:BCN7989
CAS No.:486-87-3
- N-Methylcytisine
Catalog No.:BCN1266
CAS No.:486-86-2
- Harman
Catalog No.:BCN3998
CAS No.:486-84-0
- Daidzein
Catalog No.:BCN5590
CAS No.:486-66-8
- Vasicinone
Catalog No.:BCN5589
CAS No.:486-64-6
- Isoformononetin
Catalog No.:BCN8206
CAS No.:486-63-5
- Ononin
Catalog No.:BCN5926
CAS No.:486-62-4
- Bergaptol
Catalog No.:BCN5588
CAS No.:486-60-2
- (-)-Cotinine
Catalog No.:BCC7569
CAS No.:486-56-6
- (S)-Coclaurine
Catalog No.:BCN5585
CAS No.:486-39-5
- CIQ
Catalog No.:BCC7862
CAS No.:486427-17-2
- O-Acetylcyclocalopin A
Catalog No.:BCN5586
CAS No.:486430-93-7
- Cyclocalopin A
Catalog No.:BCN5587
CAS No.:486430-94-8
- Citropten
Catalog No.:BCN4831
CAS No.:487-06-9
- Elemicin
Catalog No.:BCN2818
CAS No.:487-11-6
- Scopoline
Catalog No.:BCN1942
CAS No.:487-27-4
- Syringaresinol
Catalog No.:BCN3042
CAS No.:487-35-4
- Pinoresinol
Catalog No.:BCN5591
CAS No.:487-36-5
- Phillygenin
Catalog No.:BCN2653
CAS No.:487-39-8
- Phillyrin
Catalog No.:BCN1096
CAS No.:487-41-2
- Ononetin
Catalog No.:BCC6367
CAS No.:487-49-0
- Butein
Catalog No.:BCN5592
CAS No.:487-52-5
Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation.[Pubmed:23337038]
Bone. 2013 May;54(1):126-32.
Fracture healing is a complex interplay between endochondral and intramembranous bone formation processes. The canonical Wnt/beta-catenin pathway enhances new bone formation and may play a role in fracture healing. Glycogen synthase kinase 3beta (GSK3beta) is a key regulator of beta-catenin degradation. In this study, we investigate the effects of AZD2858, an orally bioactive GSK3 inhibitor, on fracture healing. Femoral fractures were produced in rats after the insertion of a femoral nail. The rats were treated with oral administration of AZD2858 at a dose of 30 mumol/kg (20mg/kg) daily for up to 3 weeks, while control animals were administered vehicle. At 4days, and at 1, 2 and 3 weeks, histological analysis was performed, and at the 2 and 3 week time points, we performed peripheral quantitative computed tomography (pQCT), X-rays, and four-point bending tests. Peripheral QCT showed an increase in both mineral density (of 28% at 2 weeks and 38% at 3weeks) and mineral content (of 81% at 2 weeks and 93% at 3 weeks) in the calluses from AZD2858 treated animals as compared to vehicle treated animals. Histological analysis demonstrated that rats treated with GSK3 inhibitor healed their fractures rapidly, but without the pre-formation of cartilage tissue. Furthermore, four-point bending tests of fractured femora from animals treated for 2 and 3 weeks showed an increase in strength in treated animals compared to their vehicle-treated controls. In conclusion, AZD2858, a potent GSK3 inhibitor, has a substantial impact on fracture healing. The fractures healed with a bony callus without an obvious endochondral component, suggesting that AZD2858 drives mesenchymal cells into the osteoblastic pathway. This leads to direct bone repair in an unstable fracture milieu.
