Eukaryotic initiation factor 2 (eIF2) is a key regulatory factor in protein synthesis in eukaryotic cells, relevant to the initiation step of translation. Specifically, EIF2α It is a regulatory node that controls the initiation of protein synthesis through phosphorylation or dephosphorylation. The general control of non-repressor protein 2 (GCN2), protein kinase R-like endoplasmic reticulum kinase (PERK), double stranded RNA (dsRNA) dependent protein kinase (PKR), and heme regulatory inhibitor (HRI) regulates eIF2 α Four types of phosphorylated kinases. Besides, during viral infection, the dsRNA or viral protein produced by viral proliferation activates different eIF2 α Kinases, leading to eIF2 α Phosphorylation. This will hinder the formation of the ternary tRNAMet-GTP-eIF2 complex and inhibit host or viral protein synthesis. Moreover, EIF2 α Phosphorylation inhibits global translation, thereby helping to restore protein homeostasis. Here, we will introduce an eIF2α dephosphorylation inhibitor, Salubrinal.

Salubrinal is an eIF2α Dephosphorylation Inhibitor for Osteoporosis Research.

At first, Salubrinal acts as a dual-specificity phosphatase 2 (Dusp2) inhibitor. Furthermore, Salubrinal suppresses inflammation in anti-collagen antibody-induced arthritis. Importantly, Salubrinal has antiviral activity against HSV-1 and inhibits dephosphorylation of eIF2α mediated by the HSV-1 protein ICP34.5.

Secondly, Salubrinal is a recently identified PP1 inhibitor capable to protect against endoplasmic reticulum (ER) stress in various model systems. Particularly, Salubrinal strongly synergized with proteasome inhibitors to augment apoptotic death of different leukemic cell lines.

Thirdly, Salubrinal significantly suppresses inflammation of the paws of CAIA mice. Consistent with the clinical scores, the thickening of the paws is also reduced in the Salubrinal-treated group.

Finally, Salubrinal is an eIF2α dephosphorylation inhibitor for osteoporosis research.

References:

[1] Drexler HC. PLoS One. 2009;4(1):e4161.

[2] Hamamura K, et al. Cell Signal. 2015 Apr;27(4):828-35.