MK-28是有效、选择性的PERK激动剂。MK-28在小鼠中表现出良好的药代动力学特征，且能透过血脑屏障。
MK-28 is a potent and selective PERK activator. MK-28 exhibits remarkable pharmacokinetic properties and high BBB penetration in mice[1].
MK-28 (0-100 μM) shows PERK selectivity in vitro on a 391-kinase panel and rescues cells (but not PERK-/- cells) from ER stress-induced apoptosis[1].ATF4 protein levels are increased signifcantly, up to 2.5-fold, in STHdhQ111/111 cells at high MK-28 concentration. CHOP and GADD34 mRNA levels show a signifcant increase in both cell types, up to 10- and 5-fold respectively[1].MK-28 has little or no efect on EIF2AK1 (HRI) or EIF2AK2 (PKR), but it activats EIF2AK4 (GCN2)[1]. Apoptosis Analysis[1]. Cell Line: STHdhQ111/111 cells.
MK-28 (10 mg/kg, IP, single dose) shows a maximum concentration (Cmax) of 105ng/ml and 30min half-life in plasma, 40 min afer the IP injection[1].MK-28 (1 mg/kg, IP, daily for 28 days) improves systemic function and survival in R6/2 mice and induces increased levels of eIF2α-P in the mouse brain striatum[1].MK-28 (Transient subcutaneous delivery) significantly improves motor and executive functions and delayed death onset in R6/2 mice, showing no toxicity[1]. Animal Model: R6/2 mice[1].
[1]. Javier Ganz, et al. A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models. Sci Rep. 2020 Apr 23;10(1):6875.
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