MK2: a novel molecular target for anti-inflammatory therapy

BACKGROUND: Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) is activated upon stress by p38 MAPK. MK2 is stimulated in a wide range of inflammatory conditions and its catalytic activity is required for cytokine production, cell migration and is a potential drug target for inflammatory diseases. Disruption of MK2 leads to a reduction in TNF-alpha production. MK2-mediated pro-inflammatory cytokine production has been demonstrated in several inflammatory conditions where TNF-alpha plays a role. OBJECTIVE/METHODS: We discuss the development of specific MK2 inhibitors for the treatment of inflammatory diseases. RESULTS/CONCLUSION: Inhibition of the p38 MAPK pathway may have therapeutic uses for inflammatory diseases. However, blocking p38 MAPK activation in vivo is not advisable due to toxicity, significant off-target effects, and lack of oral bioavailability. This concern may be countered by the use of MK2 inhibitors that can dissect the pathways downstream of p38 without affecting additional cellular functions.