1337532-29-2

Basic information

• Product Name: GSK2656157
• Synonyms: GSK2656157;5-[4-Fluoro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine;1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone;5-[4-Fluoro-1-[(6-methyl-2-pyridinyl)acetyl]-2,3-dihydro-1H-indol-5-yl]-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine GSK2656157;1-(5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyrid;GSK2656157(GSK-2656157)
• CAS NO: 1337532-29-2
• Molecular Formula: C23H21FN6O
• Molecular Weight: 416.4508432
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1337532-29-2.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 744.6±60.0 °C(Predicted)
• Appearance: /
• Density: 1.43±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (10 mg/ml with warming)
• PKA: 5.32±0.30(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: GSK2656157(CAS DataBase Reference)
• NIST Chemistry Reference: GSK2656157(1337532-29-2)
• EPA Substance Registry System: GSK2656157(1337532-29-2)

Safety Data

• Hazardous Substances Data: 1337532-29-2(Hazardous Substances Data)

Usage

Description

GSK2656157 (1337532-29-2) is a potent (IC50 = 0.9 nM) and selective (over 300 kinases) inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK).1,2? Inhibited growth of multiple human tumor xenografts in mice. GSK2656157 has also been found to potently inhibit RIPK1 (IC50 = 69 nM) and TNF-mediated RIPK1 kinase-dependent cell death in mouse embryonic fibroblasts.3 It prevented the loss of dendritic spines and rescued memory deficits after traumatic brain injury.4? GSK2656157 also enhanced glucose-stimulated insulin secretion in a mouse model of type 2 diabetes mellitus.5

Uses

GSK2656157 is an ATP-competitive and highly selective inhibitor of PKR-like endoplasmic reticulum kinase (PERK) enzyme activity. GSK2656157 also has anti-tumor and anti-angiogenic activity.

in vivo

assay shows that a single 50 mg/kg oral dose of gsk2656157 can completely inhibit the thr980 phosphorylation of endogenous pancreatic perk in mice. furthermore, gsk2656157 causes dose-dependent inhibition of tumor growth in human tumor xenograft models of pancreatic cancer (bxpc3, hpac and capan2) and multiple myeloma (nci-h929). among these cancers, the capan2 tumor is most sensitive [1].

References

Atkins et al. (2013) Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity; Cancer Res. 73 1993 Axten et al. (2014) Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development; ACS Med. Chem. Lett. 4 964 Rojas-Rivera et al. (2017) When PERK inhibitors turn out to be new potent RIPK1 inhibitors: critical issues on the specificity and use of GSK2606414 and GSK2656157; Cell Death Differ. 24 1100 Sen et al. (2017) Activation of PERK Elicits Memory Impairment through Inactivation of CREB and Downregulation of PSD95 After Traumatic Brain Injury; Neurosci. 37 5900 Kim et al. (2019) Specific PERK inhibitors enhanced glucose-stimulated insulin secretion in a mouse model of type 2 diabetes; Metabolism, 97 87

Upstream product

• 1337533-32-0 1,1-dimethylethyl 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate 
• 1337533-31-9 1,1-dimethylethyl 5-bromo-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate 
• 1337533-49-9 1,1-dimethylethyl (6-methyl-2-pyridinyl)acetate 
• 18368-63-3 6-chloro-2-picoline 
• 1337533-33-1 1,1-dimethylethyl 5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate 
• 1037075-45-8 1,1-dimethylethyl 4-fluoro-2,3-dihydro-1H-indole-1-carboxylate 
• 387-43-9 4-fluoroindole 
• 552866-98-5 2,3-dihydro-4-fluoro-1H-indole 

Relevant articles and documents

COMPOUNDS AND METHODS FOR TREATING INSULIN RESISTANCE SYNDROME

The present invention relates to a method of treating or preventing insulin resistance syndrome in an animal body by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof or a method of reducing activity of transcription factors of the FOXO family (Foxo 1, 3a, 4 and 6) by administering an inhibitor of protein kinase RNA-like endoplasmic reticulum kinase (PERK) gene, or a functional variant thereof, or an inhibitor of PERK protein or a functional variant thereof. The present invention also relates to different compounds and methods for using PERK gene or PERK protein.