Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) belongs to serine-threonine kinase family and is activated directly by stress and inflammatory signal through p38MAPK phosphorylation in diverse inflammatory conditions through the Toll-like receptor signaling pathway. MK2 has been thought to be a critical factor involved in the regulation of synthesis and release of pro-inflammatory (TNF-α, IL-6 and IL-1β, etc.) proteins[3]. PF-3644022 is a potent, selective, orally active and ATP-competitive MK2 inhibitor. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFalpha production with similar activity (IC50 = 160 nM). PF-3644022 blocks TNFalpha and IL-6 production in LPS-stimulated human whole blood with IC50 of 1.6 and 10.3 mM, respectively.[4]. PF-3644022 increases the expression of Arg1 and decreases iNOS. Realtime PCR revealed the increased expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2) and pro-apoptotic gene (Bax). The BMS score showed a reduced motor function of the twy/twy mice. The motor function was also enhanced with the treatment of PF-3644022[5].
PF-3644022 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SCC47 (HPV+)
50 µM
48 hours
RT increased MK2 protein phosphorylation while MK2 inhibitor alone did the opposite. Dual RT+MK2i treatment prevented RT-induced MK2 phosphorylation.
Oncogene. 2019 Nov;38(48):7329-7341
TU167 (HPV−)
50 µM
48 hours
RT increased MK2 protein phosphorylation while MK2 inhibitor alone did the opposite. Dual RT+MK2i treatment prevented RT-induced MK2 phosphorylation.
Oncogene. 2019 Nov;38(48):7329-7341
PF-3644022 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
MMTV-Her2 mice
MMTV-Her2 breast cancer model
Oral
5 μM
14 days
PF3644022 reduced Hsp27-Ser86 phosphorylation and percentage of E-cadherinhigh ducts and increased β-catenin nuclear translocation in mammary glands. PF3644022 did not alter the percentage of ducts with early lesions in mammary glands, but increased the Her2+ eDCCs in blood, bone marrow and lung.
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