Salubrinal is a potent and selective inhibitor of eukaryotic translation initiation factor 2α (eIF2α) dephosphorylation[1]. Salubrinal acts as a dual-specificity phosphatase 2 (Dusp2) inhibitor, inhibiting anti-collagen antibody-induced arthritis[2]. Salubrinal has anti-HSV-1 viral activity and inhibits the dephosphorylation of eIF2α mediated by the HSV-1 protein ICP34.5[3].
In vitro, treatment of human skin fibroblasts with Salubrinal (0-20μM) for 1h protected cells from UVB radiation-induced cell death in a dose-dependent manner and maintained intracellular Ca2+ homeostasis[4]. Treatment of bone marrow-derived cells isolated from mice with Salubrinal (1, 2, 5μM) for 6 days inhibited osteoclast differentiation and inhibited migration and adhesion of preosteoclasts in a dose- and time-dependent manner[5].
In vivo, Salubrinal (1mg/kg/day) was treated intraperitoneally in mice with traumatic brain injury (TBI) for 20 days, which effectively reduced TBI-induced plasma membrane permeability, reduced lesion volume, improved neurological deficits, and reduced ER stress-induced autophagy activation[6]. Salubrinal (1mg/kg) was treated intraperitoneally in rats with acute myocardial infarction (MI) for 30min, which increased myocardial eIF2α phosphorylation, reduced the expression of caspase-12 and C/EBP homologous protein (CHOP), and reduced myocardial cell apoptosis and infarct size[7].
References:
[1] Wang R, Sun D Z, Song C Q, et al. Eukaryotic translation initiation factor 2 subunit α (eIF2α) inhibitor salubrinal attenuates paraquat-induced human lung epithelial-like A549 cell apoptosis by regulating the PERK-eIF2α signaling pathway[J]. Toxicology In Vitro, 2018, 46: 58-65.
[2] Hamamura K, Nishimura A, Chen A, et al. Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis[J]. Cellular signalling, 2015, 27(4): 828-835.
[3] Bryant K F, Macari E R, Malik N, et al. ICP34. 5-dependent and-independent activities of salubrinal in herpes simplex virus-1 infected cells[J]. Virology, 2008, 379(2): 197-204.
[4] Ji C, Yang B, Huang S, et al. Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis[J]. Biochemical and biophysical research communications, 2017, 493(4): 1371-1376.
[5] Yokota H, Hamamura K, Chen A, et al. Effects of salubrinal on development of osteoclasts and osteoblasts from bone marrow-derived cells[J]. BMC musculoskeletal disorders, 2013, 14: 1-11.
[6] Wang Z, Gao C, Chen W, et al. Salubrinal offers neuroprotection through suppressing endoplasmic reticulum stress, autophagy and apoptosis in a mouse traumatic brain injury model[J]. Neurobiology of learning and memory, 2019, 161: 12-25.
[7] Li R J, He K L, Li X, et al. Salubrinal protects cardiomyocytes against apoptosis in a rat myocardial infarction model via suppressing the dephosphorylation of eukaryotic translation initiation factor 2α[J]. Molecular Medicine Reports, 2015, 12(1): 1043-1049.