Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C12H12N4O4S |
| Molecular Weight | 308.313 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(CNC(=O)NC2=NC=C(S2)[N+]([O-])=O)C=C1
InChI
InChIKey=YAEMHJKFIIIULI-UHFFFAOYSA-N
InChI=1S/C12H12N4O4S/c1-20-9-4-2-8(3-5-9)6-13-11(17)15-12-14-7-10(21-12)16(18)19/h2-5,7H,6H2,1H3,(H2,13,14,15,17)
| Molecular Formula | C12H12N4O4S |
| Molecular Weight | 308.313 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15315719 | http://adisinsight.springer.com/drugs/800020125Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12928438
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15315719 | http://adisinsight.springer.com/drugs/800020125
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12928438
AstraZeneca was developing the thiazole AR-AO-14418, a selective inhibitor of glycogen synthase kinase 3β (GSK-3β), for the treatment of Alzheimer's disease and major depressive disorder. AR-AO-14418 is an important research tool in as much as, at concentrations that AR-AO-14418 is able to inhibit GSK3 activity, this compound did not affect the activity of other 26 protein kinases tested, and especially does not inhibit cdc2 and cdk5, two GSK3-related kinases that are inhibited by published GSK3 inhibitors. Furthermore, AR-AO-14418 constitutes a lead compound with therapeutic potential for the treatment of AD, as well as other neurodegenerative disorders. Later preclinical studies of AR-AO-14418 were discontinued.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013-04-15 |
|
| Inhibition of GSK-3β reverses the pro-apoptotic effect of proadifen (SKF-525A) in HT-29 colon adenocarcinoma cells. | 2012-09 |
|
| Roles of glycogen synthase kinase 3 in Alzheimer's disease. | 2012-09 |
|
| Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease. | 2012-05-23 |
|
| Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011-10-30 |
|
| Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation. | 2011-09 |
|
| Glycogen synthase kinase-3β indirectly facilitates interferon-γ-induced nuclear factor-κB activation and nitric oxide biosynthesis. | 2010-12-15 |
|
| Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone. | 2010-10-06 |
|
| Colchicine-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells. | 2010-08 |
|
| A kinesin signaling complex mediates the ability of GSK-3beta to affect mood-associated behaviors. | 2010-06-22 |
|
| Rapid modulation of TRH and TRH-like peptide release in rat brain, pancreas, and testis by a GSK-3beta inhibitor. | 2010-06 |
|
| Inhibition of glycogen synthase kinase 3beta (GSK3beta) decreases inflammatory responses in brain endothelial cells. | 2010-02 |
|
| Cardioprotection leads to novel changes in the mitochondrial proteome. | 2010-01 |
|
| Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma. | 2009-12-15 |
|
| CCR7-dependent stimulation of survival in dendritic cells involves inhibition of GSK3beta. | 2009-11-15 |
|
| Glycogen synthase kinase-3beta (GSK-3beta) inhibitors AR-A014418 and B6B3O prevent human immunodeficiency virus-mediated neurotoxicity in primary human neurons. | 2009-09 |
|
| Inhibition of endothelial progenitor cell glycogen synthase kinase-3beta results in attenuated neointima formation and enhanced re-endothelialization after arterial injury. | 2009-07-01 |
|
| Exploring complex protein-ligand recognition mechanisms with coarse metadynamics. | 2009-04-09 |
|
| Epithelial cell survival by activating transcription factor 3 (ATF3) in response to chemical ribosome-inactivating stress. | 2009-03-15 |
|
| Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma. | 2009-02-01 |
|
| Elevated glycogen synthase kinase-3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. | 2009-02 |
|
| Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer. | 2008-10-01 |
|
| Antidepressant-like effect of the novel thiadiazolidinone NP031115 in mice. | 2008-08-01 |
|
| Inhibition of GSK-3 reduces infarct volume and improves neurobehavioral functions. | 2008-07-11 |
|
| Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells. | 2007-08 |
|
| Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity. | 2007-06 |
|
| Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS. | 2007-06 |
|
| Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: association with kinase activity and tumor dedifferentiation. | 2006-09-01 |
|
| The Wnt signaling pathway as a target for the treatment of neurodegenerative disorders. | 2006-01 |
|
| Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): a radiolabelled glycogen synthase kinase-3beta specific inhibitor for PET studies. | 2005-12-01 |
|
| Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells. | 2005-03-15 |
|
| AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. | 2004-12 |
|
| GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. | 2004-05 |
|
| Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. | 2003-11-14 |
|
| Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. | 2000-02 |
|
| Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice. | 1999-08 |
|
| Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. | 1993-08-15 |
Patents
Sample Use Guides
| Substance Class |
Chemical
Created
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| Record UNII |
87KSH90Q6D
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