GSK-3beta inhibitor VIII   Click here for help

GtoPdb Ligand ID: 5979

Synonyms: AR-A014418 | GSK-3b inhibitor VIII
PDB Ligand
Compound class: Synthetic organic
Comment: This is an experimental cell-permeable, ATP-competitive inhibitor of glycogen synthase kinase-3β (GSK-3β) [2].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

GSK-3beta inhibitor VIII is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 4
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 134.63
Molecular weight 308.06
XLogP 1
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES COc1ccc(cc1)CNC(=O)Nc1ncc(s1)[N+](=O)[O-]
Isomeric SMILES COc1ccc(cc1)CNC(=O)Nc1ncc(s1)[N+](=O)[O-]
InChI 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)
InChI Key YAEMHJKFIIIULI-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Bhat R, Xue Y, Berg S, Hellberg S, Ormö M, Nilsson Y, Radesäter AC, Jerning E, Markgren PO, Borgegård T et al.. (2003)
Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418.
J Biol Chem, 278 (46): 45937-45. [PMID:12928438]
3. Cai Z, Zhao Y, Zhao B. (2012)
Roles of glycogen synthase kinase 3 in Alzheimer's disease.
Curr Alzheimer Res, 9 (7): 864-79. [PMID:22272620]
4. Eldar-Finkelman H, Schreyer SA, Shinohara MM, LeBoeuf RC, Krebs EG. (1999)
Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice.
Diabetes, 48 (8): 1662-6. [PMID:10426388]
5. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
6. Hurtado DE, Molina-Porcel L, Carroll JC, Macdonald C, Aboagye AK, Trojanowski JQ, Lee VM. (2012)
Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease.
J Neurosci, 32 (21): 7392-402. [PMID:22623685]
7. Koh SH, Kim Y, Kim HY, Hwang S, Lee CH, Kim SH. (2007)
Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS.
Exp Neurol, 205 (2): 336-46. [PMID:17433298]
8. Nikoulina SE, Ciaraldi TP, Mudaliar S, Mohideen P, Carter L, Henry RR. (2000)
Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.
Diabetes, 49 (2): 263-71. [PMID:10868943]
9. Takashima A, Noguchi K, Sato K, Hoshino T, Imahori K. (1993)
Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity.
Proc Natl Acad Sci USA, 90 (16): 7789-93. [PMID:8356085]