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Chemical Structure| 1337532-29-2 Chemical Structure| 1337532-29-2

Structure of GSK2656157
CAS No.: 1337532-29-2

Chemical Structure| 1337532-29-2

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GSK2656157 displays selectivity and ATP-competitive inhibition against protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), with an IC50 of 0.9 nM.

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Product Details of GSK2656157

CAS No. :1337532-29-2
Formula : C23H21FN6O
M.W : 416.45
SMILES Code : CC1=CC=CC(CC(N2CCC3=C2C=CC(C4=CN(C)C5=NC=NC(N)=C54)=C3F)=O)=N1
MDL No. :MFCD27997885
InChI Key :PRWSIEBRGXYXAJ-UHFFFAOYSA-N
Pubchem ID :53469059

Safety of GSK2656157

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • PERK

    PERK, IC50:0.9 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
mouse primary neonatal cardiomyocytes 1 μM 6 hours GSK2656157 significantly reduced the replication of CVB3 and EMCV in mouse cardiomyocytes Nat Commun. 2024 Apr 25;15(1):3481
L929 cells 0.1 μM 30 minutes To evaluate the effect of GSK2656157 on TNF-induced RIPK1 kinase-dependent necroptosis in L929 cells, results showed that GSK2656157 significantly inhibited cell death. Cell Death Differ. 2017 Jun;24(6):1100-1110
Mouse embryonic fibroblasts (MEFs) 1 μM 30 minutes To evaluate the effect of GSK2656157 on TNF-mediated RIPK1 kinase-dependent cell death, results showed that GSK2656157 completely inhibited TNF-mediated RIPK1 kinase-dependent apoptosis and necroptosis. Cell Death Differ. 2017 Jun;24(6):1100-1110
HeLa cells 0.02-10 μM 2.5 hours GSK2656157 inhibited PERK in the nanomolar range as expected, but surprisingly activated the ISR via GCN2 at micromolar concentrations Nat Commun. 2023 Sep 8;14(1):5535
U-2 OS cells 1 µM 24 hours Inhibition of the EIF2AK3-EIF2A axis, but did not block CHMP2A depletion-induced ATF4 and ATF3 upregulation and cell death Autophagy. 2024 Feb;20(2):349-364
Neonatal rat ventricular myocytes (NRVMs) 100 nM 12 hours Inhibited phosphorylation of PERK, abolished the protective effect of melatonin on diabetic cardiomyopathy Cardiovasc Diabetol. 2024 Jan 9;23(1):19

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Zebrafish Kri1l mutant embryos Embryo immersion 20 µM From 36 hpf to 72 hpf Inhibition of PERK signaling significantly reduces autophagosome formation and restores hematopoietic function in kri1l mutant embryos Cell Res. 2015 Aug;25(8):946-62
Mice CVB3-induced myocarditis model Intraperitoneal injection 25 mg/kg/day Once daily for 5 days GSK2656157 significantly improved survival rates, reduced cardiac inflammation and immunosuppressive mMDSC, and enhanced cardiac function and antiviral responses Nat Commun. 2024 Apr 25;15(1):3481
HDPP4 transgenic mice MERS-CoV infection model Intraperitoneal injection 25 mg/kg per day Once daily for 6 days Inhibition of PERK signaling significantly alleviated MERS-CoV-induced lung damage and improved mouse survival Sci Adv. 2021 Jun 16;7(25):eabf8577
Sprague-Dawley rats Glucocorticoid-induced osteonecrosis of the femoral head model Intragastric administration 25 mg/kg Administered 8 hours before each MPS injection, for 3 days To investigate the protective effect of GSK2656157 against glucocorticoid-induced vascular injury and osteonecrosis of the femoral head, results showed that GSK2656157 significantly reduced vascular injury and the incidence of osteonecrosis. Int J Biol Sci. 2020 Jan 1;16(4):543-552
Rats Subarachnoid hemorrhage model Intracerebroventricular injection 30, 60, 120, 180, 240 or 300 μg Twice, at 8 h before and after perforation GSK2656157 significantly inhibited PERK autophosphorylation and reduced TXNIP expression in a dose-dependent manner, while improving BBB permeability and brain edema. J Neuroinflammation. 2017 May 11;14(1):104
Mice TNF-induced lethal shock model Intravenous injection 0.9 mg/kg Single injection, observed for 4 days To evaluate the protective effect of GSK2656157 on TNF-induced lethal shock, results showed that GSK2656157 significantly improved survival rates and restored normal body temperature in mice. Cell Death Differ. 2017 Jun;24(6):1100-1110
Mice C57BL/6J male mice Intraperitoneal injection 50 mg/kg Single dose, livers collected 2.5 hours post injection GSK2656157 inhibited PERK in vivo but activated the ISR via GCN2 Nat Commun. 2023 Sep 8;14(1):5535
Mice INS-1 xenograft model Intraperitoneal injection 50 mg/kg Once daily for 3 weeks Inhibition of tumor growth, reducing tumor mass by ~50% Cancer Res. 2019 Dec 15;79(24):6190-6203

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.40mL

0.48mL

0.24mL

12.01mL

2.40mL

1.20mL

24.01mL

4.80mL

2.40mL

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