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Chemical Structure| 486424-20-8 Chemical Structure| 486424-20-8

Structure of AZD2858
CAS No.: 486424-20-8

Chemical Structure| 486424-20-8

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AZD2858 is an inhibitor of GSK-3 with IC50 of 68 nM that can inhibit the tau phosphorylation of S396 site and activate Wnt signaling pathway.

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Product Details of AZD2858

CAS No. :486424-20-8
Formula : C21H23N7O3S
M.W : 453.52
SMILES Code : O=C(C1=NC(C2=CC=C(S(=O)(N3CCN(C)CC3)=O)C=C2)=CN=C1N)NC4=CC=CN=C4
MDL No. :MFCD26397072
InChI Key :FHCSBLWRGCOVPT-UHFFFAOYSA-N
Pubchem ID :10138980

Safety of AZD2858

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of AZD2858

PI3K-AKT
Hedgehog

Isoform Comparison

Biological Activity

Target
  • GSK-3

    GSK-3, IC50:68 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
PC346Flu1 1000 nM 24 hours To evaluate the inhibitory effect of AZD2858 on GSK3β and its impact on apoptosis. Results showed that AZD2858 inhibited GSK3β activity and reversed capivasertib-induced apoptosis and DNA damage. PMC11014923
C4-2 1000 nM 24 hours To evaluate the inhibitory effect of AZD2858 on GSK3β and its impact on apoptosis. Results showed that AZD2858 inhibited GSK3β activity and reversed capivasertib-induced apoptosis and DNA damage. PMC11014923
22RV1 1000 nM 24 hours To evaluate the inhibitory effect of AZD2858 on GSK3β and its impact on apoptosis. Results showed that AZD2858 inhibited GSK3β activity and reversed capivasertib-induced apoptosis and DNA damage. PMC11014923
T98G cells 1–2 μM 24 hours AZD2858 induced PRC and c-MYC protein expression by inhibiting GSK-3 activity but did not affect their in vitro proteolytic stability. PMC5207252
U2OS cells 1–2 μM 24 hours AZD2858 induced PRC and c-MYC protein expression by inhibiting GSK-3 activity but did not affect their in vitro proteolytic stability. PMC5207252
CRC cell lines (LoVo and SW620) 1 μM 24 or 48 hours To evaluate the effect of AZD2858 alone or in combination with verteporfin on CRC cell viability. Results showed that the inhibitory effect of AZD2858 was partially dependent on YAP1 activity. PMC9719955
GBM4 1.01-6.52 µM 72 hours To assess the effect of AZD2858 on cell viability, results showed cytotoxicity in the low micromolar range. PMC8657225
GBM1 1.01-6.52 µM 72 hours To assess the effect of AZD2858 on cell viability, results showed cytotoxicity in the low micromolar range. PMC8657225
U251 1.01-6.52 µM 72 hours To assess the effect of AZD2858 on cell viability, results showed cytotoxicity in the low micromolar range. PMC8657225
U87 1.01-6.52 µM 72 hours To assess the effect of AZD2858 on cell viability, results showed cytotoxicity in the low micromolar range. PMC8657225

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c Nude mice Subcutaneous xenograft model Oral gavage 10 mg/kg/day 10 days To assess the effect of AZD2858 on tumor growth, results showed growth delay in the AZD2858-treated group compared to untreated controls. PMC8657225

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

11.02mL

2.20mL

1.10mL

22.05mL

4.41mL

2.20mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[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.

[2]Sisask G, Marsell R, et al. Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation. Bone. 2013 May;54(1):126-32.

[3]GSK-3

[4] 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.

[5]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.

[6] Berg S, Bergh M, Hellberg S, Högdin K, Lo-Alfredsson Y, Söderman P, von Berg S, Weigelt T, Ormö M, Xue Y, Tucker J, Neelissen J, Jerning E, Nilsson Y, Bhat R. Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimer's disease: design, synthesis, and characterization of pyrazines. J Med Chem. 2012 Nov 8;55(21):9107-19. doi: 10.1021/jm201724m. Epub 2012 Apr 27.

[7] 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.

 

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