864388-65-8

中文名称化合物 MK-28

英文名称 Benzaldehyde, 3,4-dihydroxy-, 2-(4,6-diphenyl-2-pyrimidinyl)-2-methylhydrazone

CAS 864388-65-8

分子式 C24H20N4O2

分子量 396.44

MOL 文件 864388-65-8.mol

864388-65-8 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物 MK-28

英文别名

MK-28
Benzaldehyde, 3,4-dihydroxy-, 2-(4,6-diphenyl-2-pyrimidinyl)-2-methylhydrazone

物理化学性质

沸点658.4±65.0 °C(Predicted)

密度1.22±0.1 g/cm3(Predicted)

储存条件-20°C储存

溶解度DMSO: 12.5 mg/mL (31.53 mM)

酸度系数(pKa)8.35±0.35(Predicted)

形态Solid

颜色Light yellow to yellow

水溶解性Water: < 0.1 mg/mL (insoluble)

常见问题列表

生物活性

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。

体外研究

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.
ATF4 protein levels are increased signifcantly, up to 2.5-fold, in ST Hdh Q ^111/111 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.
MK-28 has little or no efect on EIF2AK1 (HRI) or EIF2AK2 (PKR), but it activats EIF2AK4 (GCN2).

Apoptosis Analysis.

Cell Line:	ST Hdh Q ^111/111 cells.
Concentration:	0-100 μM.
Incubation Time:	48 h.
Result:	Rescued cells from ER stress-induced apoptosis.

体内研究

MK-28 (10 mg/kg, IP, single dose) shows a maximum concentration (C _max ) of 105ng/ml and 30min half-life in plasma, 40 min afer the IP injection.
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.
MK-28 (Transient subcutaneous delivery) significantly improves motor and executive functions and delayed death onset in R6/2 mice, showing no toxicity.

Animal Model:	R6/2 mice.
Dosage:	1 mg/kg.
Administration:	IP, daily for 28 days.
Result:	Incerased the survival.