GSK2656157 | PERK inhibitor

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

References:

1. Atkins et al. (2013) Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity; Cancer Res. 73 1993
2. Axten et al. (2014) Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development; ACS Med. Chem. Lett. 4 964
3. 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
4. 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
5. Kim et al. (2019) Specific PERK inhibitors enhanced glucose-stimulated insulin secretion in a mouse model of type 2 diabetes; Metabolism, 97 87