Synonym
AZD-2858; AZD 2858; AZD2858;
IUPAC/Chemical Name
3-amino-6-[4-[(4-methyl-1-piperazinyl)sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamid
InChi Key
FHCSBLWRGCOVPT-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
NC1=NC=C(C2=CC=C(S(N3CCN(C)CC3)(=O)=O)C=C2)N=C1C(NC4=CC=CN=C4)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
AZD2858 is a potent GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively.
In vitro activity:
Further proof that GSK-3 acts through the GSK-3 sites bounded by PRC(Δ1501–1508) was obtained using AZD2858, a novel GSK-3 inhibitor developed by AstraZeneca. As observed with CCCP, AZD2858 induced PRC(FL) (Fig. 4E), a result consistent with the negative control of PRC expression by GSK-3. Interestingly, in contrast with CCCP, AZD2858 induction of PRC was not accompanied by enhanced proteolytic stability. As shown in Fig. 5A, treatment of cells with AZD2858 led to the induction of both PRC and c-MYC under conditions where the NRF-2α control was unaffected. AZD2858 decreased both GSK-3α and β expression. Cells treated with AZD2858, under conditions of maximal PRC induction, were indistinguishable morphologically from untreated cells, were mitotically active (Fig. 9A), and exhibited little loss of cell viability (Fig. 9B).
Reference: J Biol Chem. 2016 Dec 2; 291(49): 25529–25541. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207252/
In vivo activity:
In this study, the effects of AZD2858, an orally bioactive GSK3 inhibitor, were investigated 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 μmol/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, peripheral quantitative computed tomography (pQCT), Xrays, and four-point bending tests were performed. 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.
Reference: Bone. 2013 May;54(1):126-32. https://pubmed.ncbi.nlm.nih.gov/23337038/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
8.0 |
17.64 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
453.52
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Gleyzer N, Scarpulla RC. Concerted Action of PGC-1-related Coactivator (PRC) and c-MYC in the Stress Response to Mitochondrial Dysfunction. J Biol Chem. 2016 Dec 2;291(49):25529-25541. doi: 10.1074/jbc.M116.719682. Epub 2016 Oct 27. PMID: 27789709; PMCID: PMC5207252. 2. Gao L, Chen B, Li J, Yang F, Cen X, Liao Z, Long X. Wnt/β-catenin signaling pathway inhibits the proliferation and apoptosis of U87 glioma cells via different mechanisms. PLoS One. 2017 Aug 24;12(8):e0181346. doi: 10.1371/journal.pone.0181346. PMID: 28837560; PMCID: PMC5570310.
3. Gilmour PS, O'Shea PJ, Fagura M, Pilling JE, Sanganee H, Wada H, Courtney PF, Kavanagh S, Hall PA, Escott KJ. 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 Oct 15;272(2):399-407. doi: 10.1016/j.taap.2013.07.001. Epub 2013 Jul 18. PMID: 23872097.
4. Sisask G, Marsell R, Sundgren-Andersson A, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone. 2013 May;54(1):126-32. doi: 10.1016/j.bone.2013.01.019. Epub 2013 Jan 19. PMID: 23337038.
In vitro protocol:
1. Gleyzer N, Scarpulla RC. Concerted Action of PGC-1-related Coactivator (PRC) and c-MYC in the Stress Response to Mitochondrial Dysfunction. J Biol Chem. 2016 Dec 2;291(49):25529-25541. doi: 10.1074/jbc.M116.719682. Epub 2016 Oct 27. PMID: 27789709; PMCID: PMC5207252. 2. Gao L, Chen B, Li J, Yang F, Cen X, Liao Z, Long X. Wnt/β-catenin signaling pathway inhibits the proliferation and apoptosis of U87 glioma cells via different mechanisms. PLoS One. 2017 Aug 24;12(8):e0181346. doi: 10.1371/journal.pone.0181346. PMID: 28837560; PMCID: PMC5570310.
In vivo protocol:
1. Gilmour PS, O'Shea PJ, Fagura M, Pilling JE, Sanganee H, Wada H, Courtney PF, Kavanagh S, Hall PA, Escott KJ. 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 Oct 15;272(2):399-407. doi: 10.1016/j.taap.2013.07.001. Epub 2013 Jul 18. PMID: 23872097. 2. Sisask G, Marsell R, Sundgren-Andersson A, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone. 2013 May;54(1):126-32. doi: 10.1016/j.bone.2013.01.019. Epub 2013 Jan 19. PMID: 23337038.
1: Gilmour PS, O'Shea PJ, Fagura M, Pilling JE, Sanganee H, Wada H, Courtney PF, Kavanagh S, Hall PA, Escott KJ. 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 Oct 15;272(2):399-407. doi: 10.1016/j.taap.2013.07.001. Epub 2013 Jul 18. PubMed PMID: 23872097.
2: Sisask G, Marsell R, Sundgren-Andersson A, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone. 2013 May;54(1):126-32. doi: 10.1016/j.bone.2013.01.019. Epub 2013 Jan 19. PubMed PMID: 23337038.
3: Marsell R, Sisask G, Nilsson Y, Sundgren-Andersson AK, Andersson U, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone. 2012 Mar;50(3):619-27. doi: 10.1016/j.bone.2011.11.007. Epub 2011 Nov 25. PubMed PMID: 22142634.
