486424-20-8 Usage
Description
AZD-2858 is a selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 68 nM, which activates Wnt signaling and has been shown to increase bone mass in rats. It is a promising compound for the treatment of various neurological diseases due to its specific targeting of GSK-3β.
Uses
Used in Pharmaceutical Industry:
AZD-2858 is used as a therapeutic agent for the treatment of neurological diseases such as Alzheimer's. Its application is based on its ability to inhibit GSK-3β, which plays a role in the pathogenesis of these conditions.
Used in Bone Health Applications:
AZD-2858 is used as a bone mass-increasing agent in the field of bone health. AZD-2858's ability to activate Wnt signaling and increase bone mass in rats makes it a potential candidate for the treatment of conditions related to bone loss or osteoporosis.
In vitro
AZD2858 is a selective GSK-3 inhibitor with an IC50 of 68 nM, inhibits tau phosphorylation at the S396 site, activates Wnt signaling pathway. AZD2858 treatment (1 μM, 12 h) on primary isolated human osteoblast-like cells results in a 3-fold increase of β-catenin levels. AZD2858 causes β-catenin stabilisation in human and rat mesenchymal stem cells, stimulates hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro.
In vivo
In rats, oral AZD2858 treatment causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control). A small but significant effect is also seen at cortical sites (total BMC: 111% of control). AZD285 treatment (30 μmol/kg) on rats daily for up to 3 weeks shows an increase in both mineral density (of 28% at 2 weeks and 38% at 3 weeks) and mineral content (of 81% at 2 weeks and 93% at 3 weeks) in the calluses. AZD285 treatment makes the fractures heals more rapidly, with a bony callus without an obvious endochondral component. AZD2858 produces time-dependent changes in serum bone turnover biomarkers and increases bone mass over 28 days exposure in rats. After 7 days, AZD2858 increases the bone formation biomarker P1NP, and reduces the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats.
Check Digit Verification of cas no
The CAS Registry Mumber 486424-20-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,8,6,4,2 and 4 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 486424-20:
(8*4)+(7*8)+(6*6)+(5*4)+(4*2)+(3*4)+(2*2)+(1*0)=168
168 % 10 = 8
So 486424-20-8 is a valid CAS Registry Number.
486424-20-8Relevant articles and documents
Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimers Disease: Design, synthesis, and characterization of pyrazines
Berg, Stefan,Bergh, Margareta,Hellberg, Sven,Hoegdin, Katharina,Lo-Alfredsson, Yvonne,Soederman, Peter,Von Berg, Stefan,Weigelt, Tatjana,Ormoe, Mats,Xue, Yafeng,Tucker, Julie,Neelissen, Jan,Jerning, Eva,Nilsson, Yvonne,Bhat, Ratan
, p. 9107 - 9119,13 (2020/10/15)
Glycogen synthase kinase-3β, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3β localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimers disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and bloo-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimers disease.
