2BAct is an activator of eukaryotic translation initiation factor 2B (eIF2B; EC50 = 33 nM in a reporter assay).1 It enhances eIF2B activity in primary fibroblasts isolated from Eif2b5R191H mutant (R191H) mouse embryos (EC50 = 7.3 nM), a model of vanishing white matter (VWM) leukodystrophy. In vivo, 2BAct (30 mg/kg) normalizes body weight gain and prevents the development of motor deficits in R191H mice. It also prevents activation of the integrated stress response and myelin loss in the same model.
1.Wong, Y.L., LeBon, L.B., A.M., Kohlhaas, K.L., et al.eIF2B activator prevents neurological defects caused by a chronic integrated stress responseeLife8e42949(2019)