| Identification | Back Directory | [Name]
GSK2656157 | [CAS]
1337532-29-2 | [Synonyms]
CS-804
GSK2656157
GSK2656157 USP/EP/BP
GSK2656157(GSK-2656157)
PERK inhibitor GS2656157
PERK inhibitor GSK2656157
4-Dihydroxybenzoic acid methyl ester
GSK2656157; GSK 2656157; GSK-2656157.
1-(5-(4-Amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyrid
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
1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethan-1-one
GSK2656157
Ethanone, 1-[5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoro-2,3-dihydro-1H-indol-1-yl]-2-(6-methyl-2-pyridinyl)-
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 | [Molecular Formula]
C23H21FN6O | [MDL Number]
MFCD27997885 | [MOL File]
1337532-29-2.mol | [Molecular Weight]
416.451 |
| Chemical Properties | Back Directory | [Melting point ]
194-196°C | [Boiling point ]
744.6±60.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (10 mg/ml with warming) | [form ]
solid | [pka]
5.32±0.30(Predicted) | [color ]
White | [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. |
| Hazard Information | Back Directory | [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. | [Definition]
ChEBI: GSK2656157 is a pyrrolopyrimidine that is 7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine which has been substituted at position 5 by a 4-fluoro-2,3-dihydro-1H-indol-5-yl group, the nitrogen of which has been acylated by a (6-methylpyridin-2-yl)acetyl group. An orally bioavailable PERK inhibitor. It has a role as an EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor, a PERK inhibitor and an antineoplastic agent. It is a pyrrolopyrimidine, a biaryl, a member of indoles, a member of methylpyridines, an organofluorine compound and a tertiary carboxamide. | [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]. | [IC 50]
EIF2AK3 (PERK): 0.9 nM (IC50); EIF2AK1 (HRI): 460 nM (IC50); BRK: 905 nM (IC50); EIF2AK2 (PKR): 905 nM (IC50); MEKK3: 954 nM (IC50); Aurora B: 1259 nM (IC50); KHS: 1764 nM (IC50); LCK: 2344 nM (IC50); MLK2: 2796 nM (IC50); MEKK3: 2847 nM (IC50); ALK5: 3020 nM (IC50); MLCK2: 3039 nM (IC50); EIF2AK4(GCN2): 3162 nM (IC50); c-MER: 3431 nM (IC50); PI3Kγ: 3802 nM (IC50); WNK3: 5951 nM (IC50); LRRK2: 6918 nM (IC50); ROCK1: 7244 nM (IC50); MSK1: 8985 nM (IC50); NEK1: 9807 nM (IC50); AXL: 9808 nM (IC50); JAK2: 24547 nM (IC50) | [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 |
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