PERK activator MK-28 is a potent, selective small molecule PERK activator with EC50 of 490 nM.
MK-28 shows little or no effect on EIF2AK1 (HRI) or EIF2AK2 (PKR), weakly activated EIF2AK4 (GCN2) with EC50 of 3.5 uM, also displays high selectivity on a panel of 391 kinases.
MK-28 rescues cells from ER stress-induced apoptosis.
MK-28 is predicted to interact with the PERK activation loop and its cellular protective effect is PERK-dependent and more potent than CCT020312.
MK-28 exhibits brain penetrance and improves neurological functions in the R6/2 HD mouse model.
MK-28 improves systemic function and survival in R6/2 mice and induces increased levels of eIF2α-P in the mouse brain striatum.
