AZD2858_DataSheet_MedChemExpress

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Data Sheet

Product Name:Cat. No.:CAS No.:

Molecular Formula:Molecular Weight:Target:Pathway:Solubility:

AZD2858HY-15761486424-20-8C21H23N7O3S453.52GSK–3; GSK–3

Stem Cell/Wnt; PI3K/Akt/mTOR10 mM in DMSO

BIOLOGICAL ACTIVITY: 

AZD2858 is a selective GSK–3 inhibitor with an IC50 of 68 nM, inhibits tau phosphorylation at the S396 site, activates Wnt signalingpathway.

IC50 Value: 68 nM [1]Target: GSK3

in vitro: Treatment (1 μM) of human osteoblast cells with AZD2858 in vitro increased β–catenin levels after a short period of time.AZD2858 treatment (1 μM, 12 h) on primary isolated human osteoblast–like cells results in a 3–fold increase of β–catenin levels [1].in vivo: In rats, oral AZD2858 treatment caused a dose–dependent increase in trabecular bone mass compared to control after atwo–week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control; p<0.001). A small butsignificant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increasein both vertebral compression strength at a dose of 20 mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphysealstrength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01) [1]. The rats were treated withoral administration of AZD2858 at a dose of 30 μmol/kg (20mg/kg) daily for up to 3 weeks, while control animals were administeredvehicle. At 4days, and at 1, 2 and 3 weeks, histological analysis was performed, and at the 2 and 3 week time points, we performedperipheral quantitative computed tomography (pQCT), X–rays, and four–point bending tests [2].Toxicity:Clinical trial:

PROTOCOL (Extracted from published papers and Only for reference)

Animal administration [2]

Sixty–four female Sprague Dawley rats ae used. At the start of treatment, animals ae 9 weeks of age and ranged in weight from 210 to240 g. Animals ae housed individually in cages equipped with an automatic watering valve and/or water bottle. The animals aemaintained on a 12 hour light/12 hour dark cycle at 22 °C with ad libitum access to a standard certified, pelleted commerciallaboratory diet. An acclimation period of 10 days preceded treatment. On the day of surgery, the animals are weighed and randomlyassigned to treatment groups. Each rat is dosed orally with vehicle or AZD2858 solution using a steel gavage tube. The dose volume is10 mL/kg. The vehicle is deionized Milli–Q water (adjusted to pH 3.5 ± 0.1). AZD2858 is prepared by diluting the test article in thevehicle. Formulations (including vehicle) are adjusted to pH 3.5 ± 0.1 using hydrochloride. 32 rats are treated once daily with AZD2858(30 μmol/kg) and the remaining 31 rats are given vehicle. One rat died from anesthesiological complications during surgery. Thetreatment is continued for up to 3 weeks until sacrifice. Four rats from the vehicle–treated and four rats from the AZD2858–treatedgroup are sacrificed after 4 days, six rats from each group are sacrificed after 1 week, 12 from the vehicle–treated and 13 from theAZD2858–treated group are sacrificed after 2 weeks, and 9 rats from each group are sacrificed after 3 weeks.

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References:

[1]. Marsell R, et al. GSK–3 inhibition by an orally active small molecule increases bone mass in rats. Bone. 2012 Mar;50(3):619–27.

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

Caution: Product has not been fully validated for medical applications. For research use only.

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