Details of the Drug

General Information of Drug (ID: DMIM9N1)

Drug Name
AZD-1080
Indication
Disease Entry ICD 11 Status REF
Alzheimer disease 8A20 Discontinued in Phase 1 [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 334.4
Topological Polar Surface Area (xlogp) 1.8
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C19H18N4O2
IUPAC Name
2-hydroxy-3-[5-(morpholin-4-ylmethyl)pyridin-2-yl]-1H-indole-5-carbonitrile
Canonical SMILES
C1COCCN1CC2=CN=C(C=C2)C3=C(NC4=C3C=C(C=C4)C#N)O
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
InChIKey
BLTVBQXJFVRPFK-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
135564570
CAS Number
612487-72-6
TTD ID
D0MC0O

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Glycogen synthase kinase-3 beta (GSK-3B) TTRSMW9 GSK3B_HUMAN Modulator [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Alzheimer disease
ICD Disease Classification 8A20
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Glycogen synthase kinase-3 beta (GSK-3B) DTT GSK3B 1.26E-01 -0.23 -0.77
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7819).
2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021264)
3 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.
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
6 The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
7 Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
8 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
9 Company report (Neurim Pharmaceuticals)
10 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
11 Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
12 Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
13 Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.