AZD1080

GSK3βinhibitor CAS# 612487-72-6

AZD1080

Catalog No. BCC4508----Order now to get a substantial discount!

Product Name & Size Price Stock
AZD1080: 5mg $219 In Stock
AZD1080: 10mg Please Inquire In Stock
AZD1080: 20mg Please Inquire Please Inquire
AZD1080: 50mg Please Inquire Please Inquire
AZD1080: 100mg Please Inquire Please Inquire
AZD1080: 200mg Please Inquire Please Inquire
AZD1080: 500mg Please Inquire Please Inquire
AZD1080: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of AZD1080

Number of papers citing our products

Chemical structure

AZD1080

3D structure

Chemical Properties of AZD1080

Cas No. 612487-72-6 SDF Download SDF
PubChem ID 135564570 Appearance Powder
Formula C19H18N4O2 M.Wt 334.37
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 21.35 mg/mL (63.85 mM; Need ultrasonic and warming)
Chemical Name 2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile
SMILES C1COCCN1CC2=CN=C(C=C2)C3=C(NC4=C3C=C(C=C4)C#N)O
Standard InChIKey BLTVBQXJFVRPFK-UHFFFAOYSA-N
Standard InChI InChI=1S/C19H18N4O2/c20-10-13-1-3-16-15(9-13)18(19(24)22-16)17-4-2-14(11-21-17)12-23-5-7-25-8-6-23/h1-4,9,11,22,24H,5-8,12H2
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.

Biological Activity of AZD1080

DescriptionAZD1080 is a selective, orally active, brain permeable inhibitor of GSK3 with Ki values of 6.9 nM and 31 nM for human GSK3α and GSK3β, respectively.
TargetsGSK-3αGSK-3β    
IC506.9 nM (Ki)31 nM (Ki)    

Protocol

Cell experiment [1]:

Cell lines

3T3 fibroblasts engineered to stably express 4-repeat human tau

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

37oC

Applications

AZD1080 inhibits phosphorylation of human tau protein in a concatenation-dependent manner (IC50 = 324 nM). The non-selective reference GSK3 inhibitor LiCl (IC50 = 1.5 mM) indicating that AZD1080 is several orders of magnitude more potent than LiCl.

Animal experiment [1]:

Animal models

11–12 days old male and female Sprague-Dawley rats

Dosage form

AZD1080 (3 or 10 lmol/kg); oral gavage (6 mL/kg).

Application

6 h after administration of AZD1080, it inhibits the tau phosphorylation by maximal of 38±2% and 48±2% in hippocampus, indicating AZD1080 is effective at inhibiting tau phosphorylation at the P-Thr231 epitope, in a time- and dose-dependent manner in brain. In addition, AZD1080 reverses cognitive deficits in mice and rescues dysfunctional synapses.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Georgievska B, Sandin J, Doherty J et al. AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem. 2013 May;125(3):446-56.

AZD1080 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

AZD1080 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of AZD1080

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.9907 mL 14.9535 mL 29.907 mL 59.814 mL 74.7675 mL
5 mM 0.5981 mL 2.9907 mL 5.9814 mL 11.9628 mL 14.9535 mL
10 mM 0.2991 mL 1.4953 mL 2.9907 mL 5.9814 mL 7.4767 mL
50 mM 0.0598 mL 0.2991 mL 0.5981 mL 1.1963 mL 1.4953 mL
100 mM 0.0299 mL 0.1495 mL 0.2991 mL 0.5981 mL 0.7477 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.

Organizitions Citing Our Products recently

 
 
 

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
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on AZD1080

AZD1080 is a novel, potent and selective inhibitor of Glycogen synthase kinase-3β (GSK3β) with the Ki values of 6.9 nM and 31 nM, respectively [1].

AZD1080 has been reported to inhibit GSK3β by binding within the ATP pocket by means of the high resolution X-ray crystal structure. In addition, AZD1080 has been noted to suppression recombinant human GSK3α and GSK3β with the Ki values of 6.9 nM and 31 nM, respectively. AZD1080 has also shown the selectivity against other kinases with the Ki values of 1150nM, 429nM,1980nM and >10μM for cdk2, cdk5, cdk2 and Erk2, respectively. Furthermore, AZD1080 has been revealed to concentration-dependently inhibit tau phosphorylation with the IC50 value of 324nM in 3T3 cell lines. Besides, AZD1080 has exhibited the good oral bioavailability the high blood – brain barrier permeability values of 8 ×10-3cm/min in rat [1].

References:
[1] Georgievska B1, Sandin J, Doherty J, Mörtberg A, Neelissen J, Andersson A, Gruber S, Nilsson Y, Schött P, Arvidsson PI, Hellberg S, Osswald G, Berg S, Fälting J, Bhat RV. AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem. 2013 May;125(3):446-56.

Featured Products
New Products
 

References on AZD1080

AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans.[Pubmed:23410232]

J Neurochem. 2013 May;125(3):446-56.

Abnormal tau phosphorylation resulting in detachment of tau from microtubules and aggregation are critical events in neuronal dysfunction, degeneration, and neurofibrillary pathology seen in Alzheimer's disease. Glycogen synthase kinase-3beta (GSK3beta) is a key target for drug discovery in the treatment of Alzheimer's disease and related tauopathies because of its potential to abnormally phosphorylate proteins and contribute to synaptic degeneration. We report the discovery of AZD1080, a potent and selective GSK3 inhibitor that demonstrates peripheral target engagement in Phase 1 clinical studies. AZD1080 inhibits tau phosphorylation in cells expressing human tau and in intact rat brain. Interestingly, subchronic but not acute administration with AZD1080 reverses MK-801-induced deficits, measured by long-term potentiation in hippocampal slices and in a cognitive test in mice, suggesting that reversal of synaptic plasticity deficits in dysfunctional systems requires longer term modifications of proteins downstream of GSK3beta signaling. The inhibitory pattern on tau phosphorylation reveals a prolonged pharmacodynamic effect predicting less frequent dosing in humans. Consistent with the preclinical data, in multiple ascending dose studies in healthy volunteers, a prolonged suppression of glycogen synthase activity was observed in blood mononuclear cells providing evidence of peripheral target engagement with a selective GSK3 inhibitor in humans.

Role of glycogen synthase kinase-3beta inhibitor AZD1080 in ovarian cancer.[Pubmed:27051274]

Drug Des Devel Ther. 2016 Mar 18;10:1225-32.

BACKGROUND: Glycogen synthase kinase-3beta (GSK-3beta) is a multifunctional serine/threonine kinase that plays an important role in cancer tumorigenesis and progression. We investigated the role of the GSK-3beta inhibitor AZD1080 in ovarian cancer cell lines. METHODS: A2780 and OVCAR3 ovarian cancer cell lines were exposed to AZD1080, after which cell proliferation, cell cycle, invasion, and migration assays were performed. Phalloidin staining was used to observe lamellipodia formation. Reverse transcription polymerase chain reaction and Western blot were used to assess the respective mRNA and protein expression levels of GSK-3beta, CDK2, CDK1, cyclin D1, matrix metalloproteinase-9 (MMP9), and Bcl-xL. RESULTS: AZD1080 exposure suppressed ovarian cancer cell proliferation, invasion, migration, and lamellipodia formation, and induced G1 arrest, which was concentration dependent. AZD1080 also significantly downregulated GSK-3beta, CDK2, CDK1, cyclin D1, MMP9, and Bcl-xL expression at both mRNA and protein levels. CONCLUSION: Taken together, our results demonstrate that the GSK-3beta inhibitor AZD1080 suppresses ovarian cancer development and therefore may indicate a new direction for ovarian cancer treatment.

Description

AZD1080 is a potent and selective GSK3 inhibitor. AZD1080 inhibits recombinant human GSK3α and GSK3β with pKi (IC50) of 8.2 (6.9 nM) and 7.5 (31 nM), respectively.

Keywords:

AZD1080,612487-72-6,Natural Products,GSK-3, buy AZD1080 , AZD1080 supplier , purchase AZD1080 , AZD1080 cost , AZD1080 manufacturer , order AZD1080 , high purity AZD1080

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: