MK-28

• CAT Number: I044681
• CAS Number: 864388-65-8
• Molecular Formula: C24H20N4O2
• Molecular Weight: 396.44
• Purity: ≥95%
• Synonyms: 4-[(E)-[(4,6-diphenylpyrimidin-2-yl)-methylhydrazinylidene]methyl]benzene-1,2-diol
• InChI: InChI=1S/C24H20N4O2/c1-28(25-16-17-12-13-22(29)23(30)14-17)24-26-20(18-8-4-2-5-9-18)15-21(27-24)19-10-6-3-7-11-19/h2-16,29-30H,1H3/b25-16+
• InChIKey: GKOVHCFOVLXKFL-PCLIKHOPSA-N
• SMILES: CN(C1=NC(=CC(=N1)C2=CC=CC=C2)C3=CC=CC=C3)N=CC4=CC(=C(C=C4)O)O

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].
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].

Reference

[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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