865854-05-3 Usage
Uses
Different sources of media describe the Uses of 865854-05-3 differently. You can refer to the following data:
1. Tideglusib is used in the treatment of brain atrophy, and movement disorder issues.
2. Tideglusib has been used:as a reference compound in ADP-GloTM Kinase assayas an allosteric inhibitor of GSK-3β to study its effects on myocardial remodeling and angiogenesis as a differentiation agent (specifically a glycogen synthase kinase (GSK)-3β inhibitor) to convert fibroblast cells into octamer-binding transcription factor-4 (OCT4)+ and vascular endothelial growth factor receptor-2 (VEGFR-2/fetal liver kinase-1 (FLK1)+ cells
Application
Tideglusib is used in the treatment of brain atrophy, and movement disorder issues.As a reagent, Tideglusib has been used:
as a reference compound in ADP-GloTM Kinase assay
as an allosteric inhibitor of GSK-3β to study its effects on myocardial remodeling and angiogenesis
as a differentiation agent (specifically a glycogen synthase kinase (GSK)-3β inhibitor) to convert fibroblast cells into octamer-binding transcription factor-4 (OCT4)+ and vascular endothelial growth factor receptor-2 (VEGFR-2/fetal liver kinase-1 (FLK1)+ cells.
Biological Activity
Tideglusib, also known as NP031112 or NP-12, is a potent non ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3), an important kinase studied in stem cell research and neurodegenerative diseases. It is currently in clinical trials for Alzheimer′s disease and Progressive Supranuclear Palsy (PSP). Tideglusib reduces phosphorylation of the tau protein and the accumulation of amyloid plaques, reduces hippocampal and entorhinal cortex neuron loss and improves spatial memory deficits. It has also shown neuroprotective and anti-inflammatory activity in a variety of animal models.
Biochem/physiol Actions
Tideglusib, also known as NP031112 or NP-12, is a potent non ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK3), an important kinase studied in stem cell research and neurodegenerative diseases. It is currently in clinical trials for Alzheimer′s disease and Progressive Supranuclear Palsy (PSP). Tideglusib reduces phosphorylation of the tau protein and the accumulation of amyloid plaques, reduces hippocampal and entorhinal cortex neuron loss and improves spatial memory deficits. It has also shown neuroprotective and anti-inflammatory activity in a variety of animal models.
in vitro
in vitro studies showed that after the unbound tideglusib was removed from the reaction medium, the enzyme function could not be recovered. in addition, the dissociation rate constant of the reaction was as low as nearly zero. all above findings suggested that tideglusib blocked gsk-3 irreversibly. such irreversibility might be responsible for the non-competitive inhibition pattern with respect to atp of tideglusib and perhaps other structurally related compounds. [1]
in vivo
based on double transgenic mice model co-expressing human mutant app and tau, a study demonstrated that tideglusib could suppress gsk-3, reduced amyloid and tau pathologies, blocked neuronal cell death and memory deficits in vivo. [2]
IC 50
a potent, selective and irreversible non-atp-competitive gsk-3β suppressor with an ic50 of 60 nm.
references
[1]domínguez jm, fuertes a, orozco l, monte-millan md, delgado e and medina m. evidence for irreversible inhibition of glycogen synthase kinase-3 by tideglusib. j biol chem. 2012 jan; 287(2): 893-904.[2]serenóa l, coma m, rodríguez m, sánchez-ferrer p, sánchez mb, gich i, agulló jm, pérez m, avila j, guardia-laguarta c, clarimón j, lleó a, gómez-isla t. a novel gsk-3β inhibitor reduces alzheimer's pathology and rescues neuronal loss in vivo. neurobiol dis. 2009 sep; 35(3): 359-67.[3]del ser, t. phase iia
Check Digit Verification of cas no
The CAS Registry Mumber 865854-05-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,5,8,5 and 4 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 865854-05:
(8*8)+(7*6)+(6*5)+(5*8)+(4*5)+(3*4)+(2*0)+(1*5)=213
213 % 10 = 3
So 865854-05-3 is a valid CAS Registry Number.
865854-05-3Relevant articles and documents
Tideglusib and Its Analogues As Inhibitors of Staphylococcus aureus SrtA
Yang, Teng,Zhang, Tao,Guan, Xiang-Na,Dong, Ze,Lan, Lefu,Yang, Song,Yang, Cai-Guang
, p. 8442 - 8457 (2020/09/21)
Sortase A (SrtA) anchors surface proteins to the cell wall envelope, and it has attracted increasing interesting as a potential antivirulence target. Several small-molecule inhibitors for SrtA have been developed, but target validation remains largely und
Thiadiazolidinones as GSK-3 inhibitors
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Page/Page column 8, (2008/06/13)
Provided are compounds of formula I wherein R1 is an organic group having at least 8 atoms selected from C or O which is not linked directly to the N through a -C(O)- and their pharmaceutical compositions. These compounds are selective GSK-3 in
