608512-97-6

Basic information

• Product Name: 8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE
• Synonyms: 8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE;PKR INHIBITOR;6,8-Dihydro-8-(1H-imidazol-5-ylmethylene)-7H-pyrrolo[2,3-g]benzothiazol-7-one;Imidazolo-oxindole PKR inhibitor C16;GW 506033X;(Z)-8-((1H-Imidazol-4-yl)methylene)-6H-thiazolo[5,4-e]indol-7(8H)-one;InSolution? PKR Inhibitor
• CAS NO: 608512-97-6
• Molecular Formula: C13H8N4OS
• Molecular Weight: 268.29
• Mol File: 608512-97-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 674.6±55.0 °C(Predicted)
• Appearance: yellow to orange-brown/
• Density: 1.604±0.06 g/cm3(Predicted)
• Storage Temp.: ?20°C
• Solubility: DMSO: soluble12mg/mL
• PKA: 10.20±0.20(Predicted)
• Stability: Stable for 2 years from date of purchsae as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• CAS DataBase Reference: 8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE(608512-97-6)
• EPA Substance Registry System: 8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE(608512-97-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 608512-97-6(Hazardous Substances Data)

Usage

Description

8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE, also known as PKR Inhibitor, is an oxindole/imidazole derivative that acts as a selective inhibitor of the enzyme double-stranded RNA-activated protein kinase (PKR). It binds to the ATP-binding site of PKR, blocking autophosphorylation and altering its activity. PKR Inhibitor has demonstrated neuroprotective and nootropic effects in animal studies, making it a promising candidate for various applications.

Uses

Used in Pharmaceutical Industry:
8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE is used as a PKR inhibitor for its neuroprotective and nootropic effects. It protects human neuroblastoma cells against cell damage triggered by tunicamycin-mediated endoplasmic reticulum stress and prevents FADD-dependent activation of caspases and apoptosis. Intraperitoneal administration of PKR inhibitor in rats reduces phosphorylation of PKR and eIF2α in the brain, while similar administration in mice enhances long-term memory storage, including contextual and auditory long-term fear memories.
Used in Neurological Applications:
8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE is used as a neuroprotective agent for its ability to prevent neuronal damage and apoptosis. It has potential applications in the treatment of various neuropathologies, such as neurodegenerative diseases and brain injuries, by modulating the activity of PKR and its downstream signaling pathways.
Used in Cognitive Enhancement:
8-(1H-IMIDAZOL-4-YLMETHYLENE)-6,8-DIHYDRO-THIAZOLO[5,4-E]INDOL-7-ONE is used as a nootropic agent for its ability to enhance long-term memory storage and improve cognitive function. It has potential applications in the development of treatments for cognitive disorders and memory impairments, as well as in the enhancement of cognitive performance in healthy individuals.

Biochem/physiol Actions

Imidazolo-oxindole PKR inhibitor C16 is a selective inhibitor of RNA-dependent protein kinases (PKR, Eif2ak2). C16 is a first reported, potent and selective PKR inhibitor. Its inhibition effect on PKR is ATP-binding site directed. C16 specifically inhibits the apoptotic PKR/eIF2a signaling pathway without stimulating the proliferative mTOR/p70S6K signaling mechanism.

in vitro

pkr inhibitor was identified as a small molecule able to inhibit the autophosphorylation of pkr and to rescue the translation blockade induced by pkr. it was found that pkr inhibitor prevented not only pkr phosphorylation but also the activation of caspase 3 induced by ab in sh-sy5y cells. in addition, the protective effect of pkr inhibitor on the neuronal cell death induced by endoplasmic reticulum-stress in sh-sy5y cells has been reported [1].

in vivo

a previous animal study used an in-vivo model of 7-day-old rat exhibiting a high activation of brain pkr to investigate the effects of pkr inhibitor. results showed for the first time that acute systemic injection of pkr inhibitor could specifically inhibit the apoptotic pkr/eif2a signaling pathway without stimulating the proliferative mtor/p70s6k signaling mechanism [1].

IC 50

186-210 nm

References

1) Jammi et al. (2003), Small molecule inhibitors of the RNA-dependent protein kinase; Biochem. Biophys. Res. Commun., 308 50 2) Shimazawa et al. (2007), Involvement of double-stranded RNA-dependent protein kinase in ER stress-induced retinal neuron damage; Ophthalmol. Vis. Sci., 48 3729 3) Ingrand et al. (2007), The oxindole/imidazole derivative C16 reduces in vivo brain PKR activation; FEBS Lett. 581 4473 4) Tronel et al. (2014), The specific PKR inhibitor C16 prevents apoptosis and IL-1β production in an acute excitotoxic rat model with a neuroinflammatory component; Neurochem. Int. 64 73 5) Couturier et al. (2011) Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures; Neuroinflammation, 8 72